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Genomes and Genes
| Smad3SummaryGene Symbol: Smad3 Description: SMAD family member 3 Alias: AU022421, Madh3, MAD homolog 3, Smad 3, mMad3, mad3, mothers against DPP homolog 3, mothers against decapentaplegic homolog 3 Species: mouse Top Publications
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Publications
Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2Yu An Yang
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
Cancer Cell 9:445-57. 2006..We report here that forced expression of a major TGF-beta signaling transducer, Smad3, reduces susceptibility to HCC in a chemically induced murine model...
Repression of Smad3 activity by histone demethylase SMCX/JARID1CTae Dong Kim
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
Biochem Biophys Res Commun 366:563-7. 2008..Further, SMCX physically interacts with Smad3, a mediator of transforming growth factor-beta (TGF-beta), and overexpression of SMCX inhibits the ability of ..
Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine-induced hepatic fibrosis in miceGiovanni Latella
Department of Internal Medicine, GI Unit, University of L Aquila, L Aquila, Italy
Liver Int 29:997-1009. 2009..Transforming growth factor-beta (TGF-beta)/Smad3 signalling plays a central role in tissue fibrogenesis, acting as a potent stimulus of ECM accumulation.
TGF-beta signal transductionJ Massague
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Annu Rev Biochem 67:753-91. 1998..Mutations in these pathways are the cause of various forms of human cancer and developmental disorders...
NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptorGo Kuratomi
Department of Biochemistry, the Cancer Institute of the Japanese Foundation for Cancer Research JFCR, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170 8455, Japan
Biochem J 386:461-70. 2005..TGF-beta-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), ..
Requirement of Smad3 for mast cell growthMasayuki Funaba
Laboratory of Nutrition, Azabu University School of Veterinary Medicine, 1 17 71 Fuchinobe, Sagamihara, Japan
Cell Immunol 240:47-52. 2006..Doubling time of BMMC from Smad3-null mice was longer than that from wild-type (WT) mice, and the differences tended to be larger with time of ..
Receptor-associated Mad homologues synergize as effectors of the TGF-beta responseY Zhang
Department of Growth and Development, University of California at San Francisco, 94143 0640, USA
Nature 383:168-72. 1996..These results define hMAD-3 and -4 as effectors of the TGF-beta response and demonstrate a function for DPCA-4/hMAD-4 as a tumour suppressor...
Remodeling of chromatin structure within the promoter is important for bmp-2-induced fgfr3 expressionFenyong Sun
Institute of Genetic Engineering, Jinan University, PR China
Nucleic Acids Res 37:3897-911. 2009..Collectively, our study results suggest a model for BMP-2-induced FGFR3 expression in which the core promoter architecture is specifically regulated...
TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilageX Yang
Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
J Cell Biol 153:35-46. 2001..In this study, we showed that TGF-beta/Smad3 signals inhibit terminal hypertrophic differentiation of chondrocyte and are essential for maintaining articular ..
TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3D Liu
Department of Growth and Development, University of California at San Francisco, 94143, USA
Genes Dev 15:2950-66. 2001..Here we show that the TGF-beta intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 ..
Inhibition of allergen-induced airway remodeling in Smad 3-deficient miceAnnie V Le
Division of Allergy and Immunology, Scripps Clinic and Research Institute, La Jolla, CA 92037, USA
J Immunol 178:7310-6. 2007Intracellular signaling pathways that converge on Smad 3 are used by both TGF-beta and activin A, key cytokines implicated in the process of fibrogenesis...
Promoter analysis reveals critical roles for SMAD-3 and ATF-2 in expression of IL-23 p19 in macrophagesFahd Al-Salleeh
Department of Oral Biology and Nebraska Center for Virology, University of Nebraska Medical Center, Lincoln, NE 68583, USA
J Immunol 181:4523-33. 2008..Inhibition of the JNK, but also the ERK MAPK pathways decreased expression of p19. These results suggest that ATF-2 and SMAD-3 are transcription factors, which are, in addition to NF-kappaB, essential for IL-23 p19 expression...
Cox-2 inactivates Smad signaling and enhances EMT stimulated by TGF-beta through a PGE2-dependent mechanismsJason R Neil
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
Carcinogenesis 29:2227-35. 2008....
TGF-beta signaling is dynamically regulated during the alveolarization of rodent and human lungsMiguel A Alejandre-Alcázar
Department of Internal Medicine, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
Dev Dyn 237:259-69. 2008..of the TGF-beta receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3, Smad4, Smad6, and Smad7 were noted as mouse and human lungs progressed through the canalicular, saccular, and ..
Functions of mammalian Smad genes as revealed by targeted gene disruption in miceM Weinstein
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 9N105, 10 Center Drive, Bethesda, MD 20892, USA
Cytokine Growth Factor Rev 11:49-58. 2000..These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response and proper development of the skeleton...
TGF-beta signalling is regulated by Schnurri-2-dependent nuclear translocation of CLIC4 and consequent stabilization of phospho-Smad2 and 3Anjali Shukla
Laboratory of Cancer Biology and Genetics, 37 Convent Drive, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Nat Cell Biol 11:777-84. 2009..Nuclear CLIC4 associates with phospho (p)-Smad2 and p-Smad3, protecting them from dephosphorylation by nuclear phosphatases...
Abnormal mouse lung alveolarization caused by Smad3 deficiency is a developmental antecedent of centrilobular emphysemaHui Chen
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
Am J Physiol Lung Cell Mol Physiol 288:L683-91. 2005..b>Smad3 is a major downstream signal transducer in the TGF-beta pathway from the cell membrane to the nucleus...
Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-betaX Yang
Genetics of Development and Disease Branch, 10 9N105, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
EMBO J 18:1280-91. 1999b>SMAD3 is one of the intracellular mediators that transduces signals from transforming growth factor-beta (TGF-beta) and activin receptors...
Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transductionM B Datto
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
Mol Cell Biol 19:2495-504. 1999..To discern the in vivo functions of one of these Smads, Smad3, we generated mice harboring a targeted disruption of this gene...
Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3Jong Seok Kang
Department of Cell and Tissue Biology, Department of Anatomy, Programs in Cell Biology and Developmental Biology, University of California, San Francisco, CA 94143 0512, USA
EMBO J 24:2543-55. 2005..factor-beta (TGF-beta) inhibits osteoblast differentiation through inhibition of the function of Runx2 (Cbfa1) by Smad3. The mechanism through which TGF-beta/Smad3 inhibits Runx2 function has not been characterized...
Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferationSusan C McKarns
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 USA
J Immunol 172:4275-84. 2004..We used Smad3(-/-) mice to investigate a role for Smad3 in IL-2 production and proliferation in T cells...
Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory responseG S Ashcroft
Laboratory of Cell Regulation and Carcinogenesis, NCI, Bethesda, Maryland 20892 5055, USA
Nat Cell Biol 1:260-6. 1999..that, in contrast to predictions made on the basis of the ability of exogenous TGF-beta to improve wound healing, Smad3-null (Smad3ex8/ex8) mice paradoxically show accelerated cutaneous wound healing compared with wild-type mice, ..
Oocyte-secreted factor activation of SMAD 2/3 signaling enables initiation of mouse cumulus cell expansionRebecca A Dragovic
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, Medical School, University of Adelaide, Adelaide, South Australia 5005, Australia
Biol Reprod 76:848-57. 2007..This study provides evidence that the CEEF is composed of TGFB superfamily molecules that signal through SMAD 2/3 to enable the initiation of mouse cumulus expansion...
Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2Hideaki Sowa
Division of Endocrinology Metabolism, Neurology and Hematology Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 6500017, Japan
J Biol Chem 279:40267-75. 2004..In the osteoblast MC3T3-E1 cells, transforming growth factor-beta and its signaling molecule, Smad3, negatively regulated Runx2 transcriptional activity...
Distinct effects of TGF-beta 1 on CD4+ and CD8+ T cell survival, division, and IL-2 production: a role for T cell intrinsic Smad3Susan C McKarns
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 174:2071-83. 2005TGF-beta1 is critical for maintaining T cell homeostasis. Smad3 has been implicated in this regulatory process, yet the cellular targets and molecular details remain poorly understood...
Smad3 null mice develop airspace enlargement and are resistant to TGF-beta-mediated pulmonary fibrosisPhilippe Bonniaud
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Canada
J Immunol 173:2099-108. 2004..matrix (ECM) gene expression through a series of intracellular signaling molecules, including Smad2 and Smad3. We show that Smad3 null mice (knockout (KO)) develop progressive age-related increases in the size of alveolar ..
Activations of ERK1/2 and JNK by transforming growth factor beta negatively regulate Smad3-induced alkaline phosphatase activity and mineralization in mouse osteoblastic cellsHideaki Sowa
Division of Endocrinology Metabolism, Neurology and Hematology Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7 5 2 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
J Biol Chem 277:36024-31. 2002..We recently demonstrated that Smad3, a TGF-beta signaling molecule, promotes ALP activity and mineralization in MC3T3-E1 cells...
TGFbeta mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregationDong Myung Shin
Department of Biochemistry and Molecular Biology AARC, Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110 799, Korea
FASEB J 22:2498-507. 2008..stress trigger the release of TGFbeta, which subsequently activates TGase2 through the nuclear translocation of Smad3. Analysis of substrate proteins reveals that TGase2-mediated protein modification results in a decrease of protein ..
Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2E Labbe
Department of Anatomy and Cell Biology, University of Toronto, Ontario, Canada
Mol Cell 2:109-20. 1998..b>Smad3 is closely related to Smad2 but suppresses activation of the gsc promoter...
FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor beta signalsB Liu
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Mol Cell Biol 19:424-30. 1999..We have also examined the structure of the FAST-2 gene and find that it overlaps with a kinesin motor protein gene. The genes are transcribed in opposite orientations, and their transcripts overlap in the 3' untranslated region...
Smad3 mutant mice develop metastatic colorectal cancerY Zhu
Center for Developmental Biology, UT Southwestern Medical Center, Dallas, Texas 75235 9133, USA
Cell 94:703-14. 1998..TGFbeta transduces its signal to the interior of the cell via Smad2, Smad3, and Smad4. We report the cloning and targeted disruption of the mouse Smad3 gene...
Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansionSven Falk
Institute of Cell Biology, ETH Honggerberg, CH 8093 Zurich, Switzerland
Cell Stem Cell 2:472-83. 2008..Thus, TGF-beta signaling controls the size of a specific brain area, the dorsal midbrain, by antagonizing canonical Wnt signaling and negatively regulating self-renewal of neuroepithelial stem cells...
Loss of NF-kappaB control and repression of Prdx6 gene transcription by reactive oxygen species-driven SMAD3-mediated transforming growth factor beta signalingNigar Fatma
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
J Biol Chem 284:22758-72. 2009
Inhibins are the major activin ligands expressed during early thymocyte developmentPaula Licona
Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Circuito Escolar s n, Mexico DF 04510
Dev Dyn 235:1124-32. 2006..Our data indicate that Activin/Inhibin signaling could regulate the process of thymus organogenesis and early thymocyte differentiation, as it has been demonstrated for other members of the TGF-beta superfamily...
TGFbeta3 is expressed in differentiating muscle of the embryonic mouse tongueAkira Yamane
Department of Biophysics, Tsurumi University School of Dental Medicine, Yokohama 230 8501, Japan
Int J Dev Biol 54:221-6. 2010....
Development and characterization of IL-21-producing CD4+ T cellsAkira Suto
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, 260 8670 Japan
J Exp Med 205:1369-79. 2008....
The roles of transforming growth factor-β and Smad3 signaling in adipocyte differentiation and obesityYuya Tsurutani
Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
Biochem Biophys Res Commun 407:68-73. 2011We aimed at elucidating the roles of transforming growth factor (TGF)-β and Smad3 signaling in adipocyte differentiation (adipogenesis) and in the pathogenesis of obesity...
Smad3-mediated upregulation of miR-21 promotes renal fibrosisXiang Zhong
Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China
J Am Soc Nephrol 22:1668-81. 2011..Lack of Smad3, but not lack of Smad2, prevented cells from upregulating miR-21 in response to TGF-β...
Transcriptional regulation of SM22alpha by Wnt3a: convergence with TGFbeta(1)/Smad signaling at a novel regulatory elementShawn L Shafer
Washington University School of Medicine, Center for Cardiovascular Research, Internal Medicine BMD, Campus Box 8301, 660 South Euclid Ave, St Louis, MO 63110, USA
J Mol Cell Cardiol 46:621-35. 2009..RNAi "knockdown" of beta-catenin inhibited Wnt3a induction of SM22alpha. Thus, Wnt/beta-catenin signaling interacts with TGFbeta/Smad pathways to control SM22alpha gene transcription...
FoxL2 and Smad3 coordinately regulate follistatin gene transcriptionAmy L Blount
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA
J Biol Chem 284:7631-45. 2009..In gonadotropic alphaT3-1 cells, activin induces follistatin transcription primarily through the action of Smad3 at an intronic Smad-binding element (SBE1)...
Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heartPaige Snider
Cardiovascular Development Group, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA
Circ Res 102:752-60. 2008..Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease...
Transgelin is a direct target of TGF-beta/Smad3-dependent epithelial cell migration in lung fibrosisHaiying Yu
University of Giessen Lung Center, Department of Medicine II, Justus Liebig University Giessen, D 35392 Giessen, Germany
FASEB J 22:1778-89. 2008..Here, we identified the transgelin (tagln) gene as a novel immediate target of TGF-beta/Smad3-dependent gene expression in ATII cells using a Smad3 chromatin immunoprecipitation (ChIP) screen...
Filamin B represses chondrocyte hypertrophy in a Runx2/Smad3-dependent mannerLihua Zheng
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
J Cell Biol 178:121-8. 2007..Filamin B binds Smad3, which is known to interact with Runx2. Smad3 phosphorylation is increased in the mutant mice...
Redundant roles of SMAD2 and SMAD3 in ovarian granulosa cells in vivoQinglei Li
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Mol Cell Biol 28:7001-11. 2008..signaling of activins, TGF-betas, growth differentiation factor 9, and nodal converge preferentially to SMAD2 and SMAD3, the in vivo functions and redundancy of these SMADs in the ovary and female reproduction remain largely ..
The anaphase-promoting complex coordinates initiation of lens differentiationGeorge Wu
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15312, USA
Mol Biol Cell 18:1018-29. 2007..Thus, Cdh1/APC is crucial to the coordination of cell cycle progression and the initiation of lens differentiation through mediating TGF-beta-signaling-induced destruction of SnoN...
Suppressed acute phase response to LPS-induced hepatic injury in Smad3-deficient miceJia hui LI
Burn Institute of Chinese PLA, Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Mol Immunol 46:362-5. 2009..Here we report that, in contrast to the markedly enhanced inflammatory response, Smad3 gene knockout (Smad3(ex8/ex8)) mice paradoxically show suppressed hepatic acute phase response to the injury ..
Localization of TGF-beta signaling intermediates Smad2, 3, 4, and 7 in developing and mature human and mouse kidneyMiriam C Banas
Klinik und Poliklinik fur Innere Medizin II, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany
J Histochem Cytochem 55:275-85. 2007..We studied the expression of TGF-beta-receptor activated Smads (Smad2 and Smad3), the common partner Smad (Smad4), an inhibitory Smad (Smad7), and the activated (phosphorylated) Smad2 (pSmad2) ..
Reduced irradiation pulmonary fibrosis and stromal cell migration in Smad3-/- marrow chimeric miceMichael W Epperly
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
In Vivo 20:573-82. 2006..b>Smad3-/- mice display decreased ionizing irradiation-induced skin fibrosis, defective osteochondrogenesis and other ..
Transforming growth factor-beta/Smad3 signaling regulates insulin gene transcription and pancreatic islet beta-cell functionHuei Min Lin
Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
J Biol Chem 284:12246-57. 2009..We identify insulin as a TGF-beta target gene and show that the TGF-beta signaling effector Smad3 occupies the insulin gene promoter and represses insulin gene transcription...
Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expressionNguan Soon Tan
Center for Integrative Genomics, NCCR Frontiers in Genetics, University of Lausanne, 1015 Lausanne, Switzerland
EMBO J 23:4211-21. 2004..Whereas conditions that mimic the initial inflammatory events stimulate PPARbeta/delta expression, TGF-beta1/Smad3 suppresses this inflammation-induced PPARbeta/delta transcription, as seen in the late re-epithelialization/..
Loss of Smad3 in acute T-cell lymphoblastic leukemiaLawrence A Wolfraim
Laboratory of Cell Regulation and Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
N Engl J Med 351:552-9. 2004..The role of one of these intermediates--Smad3--in the pathogenesis of lymphoid neoplasia is unknown.
Lack of a role for transforming growth factor-beta in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activationT J Sullivan
Howard Hughes Medical Institute, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
Proc Natl Acad Sci U S A 98:2587-92. 2001..Also, CTLA-4 ligation equally inhibits proliferation of wild-type, TGF-beta1(-/-), and Smad3(-/-) T cells...
Essential role for Smad3 in regulating MCP-1 expression and vascular inflammationMark W Feinberg
Division of Cardiovascular Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
Circ Res 94:601-8. 2004..definitive evidence that the ability of TGF-beta(1) to inhibit MCP-1 expression is mediated via its effector Smad3. Adenoviral overexpression of Smad3 potently repressed inducible expression of endogenous MCP-1...
The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosisA J Borton
Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27708, USA
J Bone Miner Res 16:1754-64. 2001b>Smad3 is a well-characterized intracellular effector of the transforming growth factor beta (TGF-beta) signaling pathway and was implicated recently in the potentiation of vitamin D receptor (VDR)-mediated signaling...
Dynamic regulation of Smad expression during mesenchyme to epithelium transition in the metanephric kidneyLeif Oxburgh
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Mech Dev 112:207-11. 2002..Down-regulation is complete in lithium chloride induced mesenchymal condensates, indicating that Smad regulation takes place at an early stage, prior to mesenchyme to epithelium transition...
Receptor-regulated and inhibitory Smads are critical in regulating transforming growth factor beta-mediated Meckel's cartilage developmentYoshihiro Ito
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA
Dev Dyn 224:69-78. 2002..The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression...
Interaction of Smads with collagen types I, III, and VLeslie R Ellis
Department of Molecular, Cellular, and Craniofacial Biology, ULSD, University of Louisville Birth Defects Center, Louisville, KY 40292, USA
Biochem Biophys Res Commun 310:1117-23. 2003..we have identified three types of collagens (types I, III, and V) that are capable of binding to the MH2 domain of Smad 3. These interactions were confirmed by glutathione S-transferase (GST) pull-down assays in which the MH2 domain of ..
Transforming growth factor-beta inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation functionLisa Choy
Department of Growth and Development, Programs in Cell Biology and Developmental Biology, University of California, San Francisco, California 94143 0640, USA
J Biol Chem 278:9609-19. 2003..Because TGF-beta inhibits adipogenesis by signaling through Smad3, we examined physical and functional interactions of Smad3 and Smad4 with C/EBPbeta, C/EBPdelta, and PPARgamma2...
Identification of three novel Smad binding proteins involved in cell polarityDennis R Warner
University of Louisville Birth Defects Center, Department of Molecular, Cellular, and Craniofacial Biology, University of Louisville School of Dentistry, 501 South Preston Street, Suite 301, Louisville, KY 40292, USA
FEBS Lett 539:167-73. 2003A yeast two-hybrid screen was utilized to identify novel Smad 3 binding proteins expressed in developing mouse orofacial tissue...
Divergence of epidermal growth factor - transforming growth factor beta signaling in embryonic orofacial tissueVasker Bhattacherjee
University of Louisville Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville School of Dentistry, Louisville, Kentucky 40292, USA
In Vitro Cell Dev Biol Anim 39:257-61. 2003..of embryonic maxillary mesenchymal cells revealed that TGFbeta-induced nuclear translocation of Smad 2 and Smad 3 proteins was not affected by EGF...
Abrogation of Smad3 and Smad2 or of Smad4 gene expression positively regulates murine embryonic lung branching morphogenesis in cultureJ Zhao
Department of Surgery, Children s Hospital Los Angeles Research Institute, University of Southern California Schools of Dentistry and Medicine, Los Angeles 90033, USA
Dev Biol 194:182-95. 1998..Antisense oligodeoxynucleotides were designed to attenuate Smad3 and Smad2 gene expression in embryonic (E11) mouse lungs over 4 days in culture...
Loss of Smad3 modulates wound healingG S Ashcroft
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cytokine Growth Factor Rev 11:125-31. 2000..Both Smad3 and its closely related homolog Smad2 act as latent nuclear transcriptional activators and mediate intracellular ..
Genetic events and the role of TGF beta in epithelial tumour progressionR J Akhurst
Onyx Pharmaceuticals, Richmond, CA 94806, USA
J Pathol 187:82-90. 1999..It is this latter effect which may be clinically more significant, since many human tumours overexpress TGF beta, yet the majority still retain the intracellular signaling systems necessary for the cell to respond to this growth factor...
Induction of vascular smooth muscle alpha-actin gene transcription in transforming growth factor beta1-activated myofibroblasts mediated by dynamic interplay between the Pur repressor proteins and Sp1/Smad coactivatorsSukanya V Subramanian
Department of Physiology and Cell Biology, Dorothy M Davis Heart and Lung Research Institute, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA
Mol Biol Cell 15:4532-43. 2004..Interplay between Pur repressor isoforms and Sp1 and Smad coactivators may regulate SMA enhancer output in TGFbeta1-activated myofibroblasts during episodes of wound repair and tissue remodeling...
Immunohistochemical expression of Smads 1-6 in the 15-day gestation mouse embryo: signaling by BMPs and TGF-betasK C Flanders
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892 5055, USA
Dev Dyn 220:141-54. 2001..Differences are observed in the nuclear versus cytoplasmic localization among the Smads in different cell types or tissues, suggesting selective activation of Smads during this stage of development...
Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cellsMarcela Guzman-Ayala
Mammalian Neurogenesis, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
PLoS ONE 4:e4268. 2009..The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFbeta signalling: they are activated by receptors, enter the ..
Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cellsLing Lu
Division of Rheumatology, Department of Medicine, Saban Research Institute, Children s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
J Immunol 184:4295-306. 2010..In this study, we report that neither Smad2 nor Smad3 gene deficiency abrogates TGF-beta-dependent iTreg induction by a deacetylase inhibitor trichostatin A in vivo, ..
Essential role of plasminogen activator inhibitor type-1 in radiation enteropathyFabien Milliat
Laboratory of Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay aux Roses Unité Propre de Recherche et de l Enseignement Supérieur, Equipe d Accueil 2710, France
Am J Pathol 172:691-701. 2008..In vitro, irradiation increased PAI-1 expression in endothelial cells by a p53/Smad3-dependent mechanism...
Mechanism of chronic aristolochic acid nephropathy: role of Smad3Li Zhou
1Department of Medicine, University of Hong Kong, Hong Kong SAR, China
Am J Physiol Renal Physiol 298:F1006-17. 2010..The present study tested the hypothesis that transforming growth factor (TGF)-beta/Smad3 may be a key pathway leading to chronic AAN...
CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsivenessCiriaco A Piccirillo
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
J Exp Med 196:237-46. 2002..Responder T cells from Smad3(-/-) or dominant-negative TGF-beta type RII transgenic (DNRIITg) mice, that are both unresponsive to TGF-beta1-..
Age and time of day influences on the expression of transforming growth factor-beta and phosphorylated SMAD3 in the mouse suprachiasmatic and paraventricular nucleiAmy L Beynon
Neuroscience and Molecular Psychiatry, Institute of Life Science, School of Medicine, Swansea University, Swansea, UK
Neuroimmunomodulation 16:392-9. 2009..we examined the expression of transforming growth factor (TGF)-beta and the associated signaller phosphorylated SMAD3 (pSMAD3) in the SCN and the paraventricular nucleus (PVN) of the hypothalamus of the young and older mouse across ..
Using RNA interference to identify the different roles of SMAD2 and SMAD3 in NIH/3T3 fibroblast cellsRong Zheng
Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, P R China
Cell Biochem Funct 26:548-56. 2008..We firstly examined the expression of Smad2 and Smad3 induced by TGF-beta 1 in normal NIH/3T3 cells...
A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transitionTheresa Vincent
Ludwig Institute for Cancer Research, Stockholm Branch, 17177 Stockholm, Sweden
Nat Cell Biol 11:943-50. 2009..Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT...
Induction of an osteoarthritis-like phenotype and degradation of phosphorylated Smad3 by Smurf2 in transgenic miceQiuqian Wu
Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York 14642, USA
Arthritis Rheum 58:3132-44. 2008..To determine whether Smurf2, an E3 ubiquitin ligase known to inhibit transforming growth factor beta (TGFbeta) signaling, is expressed in human osteoarthritic (OA) cartilage and can initiate OA in mice...
Focal adhesion kinase is required for neural crest cell morphogenesis during mouse cardiovascular developmentAinara Vallejo-Illarramendi
Department of Physiology, UCSF, San Francisco, California 94158 2611, USA
J Clin Invest 119:2218-30. 2009..Our results indicate that FAK plays an essential role in cardiac outflow tract development by promoting the activation of molecules such as Crkl and Erk1/2...
Smad3 is required for normal follicular follicle-stimulating hormone responsiveness in the mouseXiaoyan Gong
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, USA
Biol Reprod 81:730-8. 2009..Herein, we investigated the role of Smad3, a critical molecule mediating the intracellular TGFbeta family proteins, in follicle development and the ..
SOCS3 promotes TLR4 response in macrophages by feedback inhibiting TGF-beta1/Smad3 signalingXia Liu
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, People s Republic of China
Mol Immunol 45:1405-13. 2008..The functional relationship between SOCS3 and TGF-beta1/Smad3 pathway in TLR4 response also remains unclear...
BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding proteinGaoxiang Ge
Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
J Cell Biol 175:111-20. 2006..TGFbeta1 is a potent inducer of ECM formation and of BMP1 expression. Thus, a role for BMP1-like proteinases in TGFbeta1 activation completes a novel fast-forward loop in vertebrate tissue remodeling...
Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle-stimulating hormone beta subunit in mouse gonadotrope cellsDaniel J Bernard
Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10021, USA
Mol Endocrinol 18:606-23. 2004..Because SMAD7 functions by preventing access of SMAD2 and SMAD3 to ALK4, these data suggested that both activins and ALK4 require SMAD2 and/or SMAD3 to affect FSHbeta ..
Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasisAnita B Roberts
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892 5055, USA
Cytokine Growth Factor Rev 17:19-27. 2006..We used mice with a targeted deletion of Smad3 to study the specific contributions of this signaling pathway to pathogenic effects of TGF-beta...
Myofibroblast transdifferentiation in obliterative bronchiolitis: tgf-beta signaling through smad3-dependent and -independent pathwaysA M Ramirez
Andrew J McKelvey Lung Transplantation Center, Emory University School of Medicine, Atlanta, Georgia, USA
Am J Transplant 6:2080-8. 2006We have shown that Smad3, an intracellular signal transducer for transforming growth factor-beta1 (TGF-beta1), is required to elicit the full histological manifestations of obliterative airway disease in a tracheal transplant model...
Concentration-dependent bifunctional effect of TGF-beta 1 on immunoglobulin production: a role for Smad3 in IgA production in vitroSusan C McKarns
Department of Pharmacology and Toxicology, 315 National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA
Int Immunopharmacol 3:1761-74. 2003..We further investigated a putative mechanistic role for Smad3, an intracellular mediator of TGF-beta(1) signaling, in propagating the inhibitory effects of TGF-beta(1) on ..
Full-thickness wounding of the mouse tail as a model for delayed wound healing: accelerated wound closure in Smad3 knock-out miceVincent Falanga
Department of Dermatology, Roger Williams Medical Center, Elmhurst Building, 50 Maude Street, Providence, RI 02908, USA
Wound Repair Regen 12:320-6. 2004..mouse wounds that require up to 3 weeks or more for complete closure, and we show the validity of this model in Smad3 null mice, which are known to display accelerated healing. Full-thickness wounds, measuring 0.3 by 1...
[The effects of the Smad3-knockout on the hematopoiesis of mouse]Ling Zhang
State Key Lab of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China
Sheng Wu Gong Cheng Xue Bao 19:428-32. 2003The effects of the Smad3- knockout on the hematopoiesis of mouse were investigated in this work. Five pairs of wild type and Smad3- null mice were studied...
Smad3 deficiency in mast cells provides efficient host protection against acute septic peritonitisYutaka Kanamaru
Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan
J Immunol 174:4193-7. 2005..Here we determined whether Smad3, a major signal transducer of TGF-beta, regulates innate immune response by mast cells against Gram-negative ..
Essential roles of inhibin beta A in mouse epididymal coilingJessica Tomaszewski
Department of Biology, School of Integrative Biology, University of Illinois at Urbana Champaign, Urbana, IL 61802, USA
Proc Natl Acad Sci U S A 104:11322-7. 2007..These results demonstrated that Inhba, a mesenchyme-specific gene, acts collectively with testosterone to facilitate epididymal coiling by stimulating epithelial proliferation...
Selective reduction of fibrotic markers in repairing corneas of mice deficient in Smad3Brian M Stramer
Evelyn F and William L McKnight Vision Research Center, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida 33101, USA
J Cell Physiol 203:226-32. 2005..Expression of fibrotic markers in repairing cutaneous wounds is reduced in mice lacking Smad3, a downstream cytoplasmic mediator of TGF-beta signaling (Ashcroft et al., 1999, Nat Cell Biol 1(5):260-266)...
Aberrant Toll receptor expression and endotoxin hypersensitivity in mice lacking a functional TGF-beta 1 signaling pathwayNancy McCartney-Francis
Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 172:3814-21. 2004..TLR4 mRNA expression observed in TGF-beta1 null mice as well as in mice lacking the TGF-beta transcription factor Smad3 was associated with LPS hyperresponsiveness leading to increased expression of inflammatory cytokines and NO and ..
Transforming growth factor-{beta}-inducible phosphorylation of Smad3Guannan Wang
Center for Advanced Biotechnology and Medicine
J Biol Chem 284:9663-73. 2009..Upon TGF-beta treatment, the highly homologous Smad2 and Smad3 are phosphorylated by the TGF-beta receptor at the SSXS motif in the C-terminal tail...
Role of steroid receptor coactivators in glucocorticoid and transforming growth factor beta regulation of plasminogen activator inhibitor gene expressionGangyong Li
Department of Human Genetics, Box 0618, University of Michigan Medical School, Ann Arbor, Michigan 48109 0618, USA
Mol Endocrinol 20:1025-34. 2006..human hepatoma cells and that it interacts functionally and physically with the C-terminal activation domain of Smad3, a mediator of TGFbeta signaling...
Multidirectional and multizonal tangential migration of GABAergic interneurons in the developing cerebral cortexDaisuke H Tanaka
Graduate School of Frontier Biosciences, Osaka University, Japan Science and Technology Corporation, Japan
Development 133:2167-76. 2006..The MDT migration in the MZ may disperse and intermix interneurons within the cortex, resulting in a balanced distribution of interneuron subtypes...
Transforming growth factor-beta-induced differentiation of smooth muscle from a neural crest stem cell lineShiyou Chen
Department of Cell Biology, Georgetown University Medical School, Washington, DC 20057, USA
Circ Res 94:1195-202. 2004..Examination of the signaling pathways involved revealed that TGF-beta activation of Smad2 and Smad3 appear to be essential for the observed differentiation...
Small interfering RNA (siRNA) targetted to Smad3 inhibits transforming growth factor-beta signalingSeon Yong Yeom
Department of Microbiology, College of Natural Sciences, Kangwon National University, Chunchon 200 701, Republic of Korea
Biotechnol Lett 26:699-703. 2004..To determine the effect of Smad3 on transforming growth factor-beta signaling, we constructed a small interfering RNA (siRNA) targeted to Smad3...
TGF-beta signaling by Smad proteinsK Miyazono
Department of Biochemistry, the Cancer Institute of the Japanese Foundation for Cancer Research JFCR, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo, Japan
Cytokine Growth Factor Rev 11:15-22. 2000..Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types...
Smad3 mediates TGF-beta1 induction of VEGF production in lung fibroblastsTetsu Kobayashi
University of Nebraska Medical Center, Omaha, NE, USA
Biochem Biophys Res Commun 327:393-8. 2005..We examined the effect of TGF-beta1 on VEGF production by fibroblasts from mice lacking expression of Smad2 or Smad3 as well as human lung fibroblasts treated with or without Smad2 or Smad3 siRNA...
Unique and redundant roles of Smad3 in TGF-beta-mediated regulation of long bone development in organ cultureJesus Alvarez
Department of Cell Biology, University of Alabama at Birmingham, 35294, USA
Dev Dyn 230:685-99. 2004..mechanism of TGF-beta signaling in the perichondrium, we tested the hypothesis that TGF-beta-restricted Smad2 and Smad3 regulate chondrocyte proliferation and differentiation in embryonic metatarsal organ cultures...
Can't get no SMADisfaction: Smad proteins as positive and negative regulators of TGF-beta family signalsJ L Christian
Department of Cell and Developmental Biology, Oregon Health Sciences University, School of Medicine, Portland 97201 3098, USA
Bioessays 21:382-90. 1999..Negative feedback circuits such as these play important roles in fine-tuning the activity of multifunctional signaling molecules during embryonic patterning and in response to pathologic stimuli in adults...
Axin and GSK3- control Smad3 protein stability and modulate TGF- signalingXing Guo
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
Genes Dev 22:106-20. 2008..of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully understood how the baseline properties of Smad3 are regulated, although this molecule is in ..
Interference with TGF-beta signaling by Smad3-knockout in mice limits diabetic glomerulosclerosis without affecting albuminuriaAmy Wang
Division of Nephrology, Northwestern University, 303 E Chicago Ave, Tarry 4 755, Chicago, IL 60611, USA
Am J Physiol Renal Physiol 293:F1657-65. 2007..To isolate the contribution of one of the signaling pathways of TGF-beta, the Smad3 gene in the mouse was knocked out at exons 2 and 3, and the effect was studied in streptozotocin (STZ)-induced ..
Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen speciesDalliah Black
Department of Surgery, 4024 Burnett Womack Building, CB 7050, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Biochimie 89:1464-73. 2007..hepatocytes did not generate ROS activity, exhibit MPT, activate caspases, or undergo apoptosis when compared to Smad 3 (+/+) hepatocytes...
Altered gene expression in articular chondrocytes of Smad3(ex8/ex8) mice, revealed by gene profiling using microarraysHao Wang
Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China
J Genet Genomics 34:698-708. 2007It has been previously reported that small mother against decapentaplegic 3 (Smad3) gene knockout (Smad3(ex8/ex8)) mice displays phenotypes similar to human osteoarthritis, as characterized by abnormal hypertrophic differentiation of ..
Research Grants
- Mapping Murine Regeneation GenesELLEN S HEBER KATZ; Fiscal Year: 2009..Our study of regenerative healing using the well-defined LGXSM mouse resource enables us to realize the promising potential of this genetically powerful and unique healing model system. ..
- Role of Smad3 in Obliterative BronchiolitisAllan Ramirez; Fiscal Year: 2007..These findings led us to the hypothesis that activation of TGFp1/Smad3 signaling in airway fibroblasts is a critical driver of myofibroblast transdifferentiation in OB that is ..
- Renal Protection With A1 Adenosine ReceptorsH Lee; Fiscal Year: 2007..This, in turn, will contribute to improved therapeutic regimens for the protection of renal function in patients. ..
- Basic research training in embryonic developmentJan Christian; Fiscal Year: 2007..One outstanding feature of the training program at OHSU is the high level of interactions and collaborations that occur among faculty members with diverse research interests and expertise. ..
- The New Stem Cell BiologyVincent Falanga; Fiscal Year: 2007..This grant also has real promise in expanding our understanding of stem cell plasticity and stem cell transcriptional regulation and developing pre-clinical models for wound healing and muscular dystrophy. ..
- Analysis of BMP-4 activity in Cleavage mutant miceJan Christian; Fiscal Year: 2007..Understanding the molecular mechanisms by which BMP activity is regulated is key to understanding, treating and preventing congenital anomalies and diseases. ..
- Tissue Engineering for the Treatment of Delayed HealingVincent Falanga; Fiscal Year: 2007..These studies will advance our understanding of how to reconstitute the wound bed and whether it is possible to correct the abnormal cellular phenotype in non-healing wounds. ..
- Control of Hox gene expression and neuronal identityJeh Ping Liu; Fiscal Year: 2007....
- Mechanism of renal protection with volatile anestheticsH Thomas Lee; Fiscal Year: 2010..Our studies will mechanistically advance our understanding of volatile anesthetic-mediated renal tubule protection, leukocyte modulation and improved outcome after renal IR injury. ..
- KLF10, T regulatory cells, and atherogenesisMark W Feinberg; Fiscal Year: 2010..The experiments proposed in this study will examine in detail the mechanisms by which KLF10 induces the T regulatory cell suppressive phenotype and its role in experimental atherosclerosis in vivo. ..
- Mapping Murine Regeneation GenesELLEN S HEBER KATZ; Fiscal Year: 2009..Our study of regenerative healing using the well-defined LGXSM mouse resource enables us to realize the promising potential of this genetically powerful and unique healing model system. ..
- New Approaches to Tissue RepairVincent Falanga; Fiscal Year: 2009....
- Analysis of BMP-4 activity in Cleavage mutant miceJan Christian; Fiscal Year: 2004..Gain or loss of function of BMP-4 activity leads to structural birth defects. Thus, understanding how BMP activity is regulated in vivo is key to treating and preventing congenital anomalies. ..
- Inhibition of Macrophage Activation by Smad3Mark Feinberg; Fiscal Year: 2005..We found that a single member of the Smad family. Smad3-is critical for inhibiting markers of macrophage activation...
- Fucosylated cell surface molecules in tumor invasionSTEVEN DOMINO; Fiscal Year: 2005..tumors in mice carrying germline inactivating mutations in the transforming growth factor-beta signaling gene Smad3. 3) To test the importance of alpha(1,2)fucosylated oligosaccharides in colon cancer in vivo by determining the ..
- PROTECTIVE EFFECTS OF ADENOSINE RECEPTOR MODULATIONH Lee; Fiscal Year: 2005..This, in turn, will contribute to improved therapeutic regimens for the protection of renal function in patients. ..
- PATHOGENIC MECHANISMS OF VENOUS DISEASEVincent Falanga; Fiscal Year: 2004..The proposed studies should advance knowledge of the pathogenesis of venous ulceration and fibrosis. ..
- Mechanism of renal protection with volatile anestheticsH Lee; Fiscal Year: 2007..abstract_text> ..
