SMAD6

Summary

Gene Symbol: SMAD6
Description: SMAD family member 6
Alias: AOVD2, HsT17432, MADH6, MADH7, mothers against decapentaplegic homolog 6, MAD homolog 6, SMAD, mothers against DPP homolog 6, mothers against decapentaplegic, drosophila, homolog of, 6
Species: human
Products:     SMAD6

Top Publications

  1. Miyazono K. TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000;11:15-22 pubmed
    ..Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types. ..
  2. Osawa H, Nakajima M, Kato H, Fukuchi M, Kuwano H. Prognostic value of the expression of Smad6 and Smad7, as inhibitory Smads of the TGF-beta superfamily, in esophageal squamous cell carcinoma. Anticancer Res. 2004;24:3703-9 pubmed
    ..The expression of Smad6 and Smad7 as negative regulators was examined, to investigate the further effects of TGF-B superfamily signaling...
  3. Topper J, Cai J, Qiu Y, Anderson K, Xu Y, Deeds J, et al. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc Natl Acad Sci U S A. 1997;94:9314-9 pubmed
    ..Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7, encoding members of the MAD-related family of molecules, selectively induced in cultured human vascular ..
  4. Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, et al. Smad6 inhibits signalling by the TGF-beta superfamily. Nature. 1997;389:622-6 pubmed
    ..Here we report the isolation of Smad6 in the mouse...
  5. Hata A, Lagna G, Massague J, Hemmati Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 1998;12:186-97 pubmed
    ..Here we report the existence of a natural inhibitor of this process, Smad6, a longer version of the previously reported JV15-1...
  6. Afrakhte M, Moren A, Jossan S, Itoh S, Sampath K, Westermark B, et al. Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members. Biochem Biophys Res Commun. 1998;249:505-11 pubmed
    b>Smad6 and Smad7 function as intracellular antagonists in transforming growth factor-beta (TGF-beta) signaling. Here we report the isolation of human Smad6, which is closely related to Smad7...
  7. Galvin K, Donovan M, Lynch C, Meyer R, Paul R, Lorenz J, et al. A role for smad6 in development and homeostasis of the cardiovascular system. Nat Genet. 2000;24:171-4 pubmed
    ..Here we explore the role of an inhibitory Smad in vivo by targeted mutation of Madh6 (which encodes the Smad6 protein)...
  8. Bai S, Shi X, Yang X, Cao X. Smad6 as a transcriptional corepressor. J Biol Chem. 2000;275:8267-70 pubmed
    b>Smad6 and Smad7, a subgroup of Smad proteins, antagonize the signals elicited by transforming growth factor-beta...
  9. Murakami G, Watabe T, Takaoka K, Miyazono K, Imamura T. Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol Biol Cell. 2003;14:2809-17 pubmed
    ..Herein, we examined whether Smurf1 negatively regulates BMP signaling together with the I-Smads Smad6/7. Smurf1 and Smad6 cooperatively induced secondary axes in Xenopus embryos...

More Information

Publications156 found, 100 shown here

  1. Yin J, Lu K, Lin J, Wu L, Hildebrandt M, Chang D, et al. Genetic variants in TGF-β pathway are associated with ovarian cancer risk. PLoS ONE. 2011;6:e25559 pubmed publisher
    ..Individual SNP analysis showed that the most significant SNP was SMAD6: rs4147407, with an adjusted odds ratio (OR) of 1.60 (95% confidence interval [CI], 1.14-2.24, P = 0...
  2. Dogar A, Pauchard Batschulat R, Grisoni Neupert B, Richman L, Paillusson A, Pradervand S, et al. Short-lived AUF1 p42-binding mRNAs of RANKL and BCL6 have two distinct instability elements each. PLoS ONE. 2018;13:e0206823 pubmed publisher
    ..Still, some enriched mRNAs were highly unstable, as those of TNFSF11 (known as RANKL), KLF10, HES1, CCNT2, SMAD6, and BCL6. We have mapped some of the instability determinants...
  3. Chasapis C, Kandias N, Episkopou V, Bentrop D, Spyroulias G. NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase. Proteins. 2012;80:1484-9 pubmed publisher
    ..Ub) ligase, amplifies TGF-β signaling responses by targeting for degradation of the negative regulators Smad6/7 and the SnoN/Ski transcriptional repressors when they block the TGF-β effectors Smad2/3...
  4. Du C, Pan P, Jiang Y, Zhang Q, Bao J, Liu C. Microarray data analysis to identify crucial genes regulated by CEBPB in human SNB19 glioma cells. World J Surg Oncol. 2016;14:258 pubmed
    ..adhesion (which involved THBS1 and THBS2), TGF-beta signaling pathway (which involved THBS1, THBS2, SMAD5, and SMAD6) and chronic myeloid leukemia (which involved TGFBR2 and CCND1)...
  5. Kloth K, Bierhals T, Johannsen J, Harms F, Juusola J, Johnson M, et al. Biallelic variants in SMAD6 are associated with a complex cardiovascular phenotype. Hum Genet. 2019;: pubmed publisher
    Rare heterozygous variants in SMAD6 have been identified as a significant genetic contributor to bicuspid aortic valve-associated thoracic aortic aneurysm on one hand and non-syndromic midline craniosynostosis on the other...
  6. Gouttenoire J, Bougault C, Aubert Foucher E, Perrier E, Ronzière M, Sandell L, et al. BMP-2 and TGF-beta1 differentially control expression of type II procollagen and alpha 10 and alpha 11 integrins in mouse chondrocytes. Eur J Cell Biol. 2010;89:307-14 pubmed publisher
    ..In addition, adenoviral expression of Smad6, an inhibitor of BMP canonical Smad signaling, did not affect expression of total type II procollagen or the ratio ..
  7. Kawahara T, Yamashita M, Ikegami K, Nakamura T, Yanagita M, Yamada S, et al. TGF-Beta Negatively Regulates the BMP2-Dependent Early Commitment of Periodontal Ligament Cells into Hard Tissue Forming Cells. PLoS ONE. 2015;10:e0125590 pubmed publisher
    ..Quantitative reverse transcription polymerase chain reaction analysis revealed that the expressions of Smurf1 and Smad6, which are negative feedback components in the TGF-β/BMP signaling pathway, were downregulated in MPDL22 cells ..
  8. Brown J, Ollier W, Arscott G, Ke X, Lamb J, Day P, et al. Genetic susceptibility to keloid scarring: SMAD gene SNP frequencies in Afro-Caribbeans. Exp Dermatol. 2008;17:610-3 pubmed publisher
    ..Identification of genetic markers in candidate genes such as the SMAD family may be of significant importance in diagnosis, prognosis and development of new therapies in the management of keloid scarring. ..
  9. Fujisawa S, Komatsubara M, Ogura Ochi K, Tsukamoto Yamauchi N, Toma K, Inagaki K, et al. Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells. Peptides. 2019;113:35-40 pubmed publisher
    ..Orexin A also reduced ALK-3 expression but increased inhibitory Smad6/7 expression, while BMP-4 treatment downregulated OX1R expression...
  10. Mei C, Zhang L, Fan Z, Song Y, Zhang M, Liu H. The effects of Smad6 via small RNA pathways on the ischemic injury in PC12 cells. Clin Lab. 2014;60:2063-71 pubmed
    ..the neuroprotective effect of exogenous ActA on oxygen-glucose deprivation (OGD) injury, the endogenous role of Smad6 remains not well understood...
  11. Wang C, Yu T, Tan L, Cheng J. Bioinformatics analysis of gene expression profile in callus tissues of osteoporotic phenotype mice induced by osteoblast-specific Krm2 overexpression. Int J Rheum Dis. 2016;19:1263-1271 pubmed publisher
    ..Other hub nodes, such as Ccnb2 and Rrm2, were closely associated with the p53 signaling pathway. Tal1 and Smad6 were found to be differentially expressed transcription factors...
  12. Li G, Liu X, Li X, Gao Z, Huang L, Liu Y. [Regulations of berberine on gene expression of BMP4 transcriptional pathways to improve visceral white adipose tissues insulin resistance in type 2 diabetic hamsters]. Zhongguo Zhong Yao Za Zhi. 2016;41:514-520 pubmed publisher
    ..p38/MAPK, ATF2, PRDM16, C/EBP?, PGC1?, PPAR? and brown adipose tissue-specific genes was decreased and that of Smad6, Smurf1 and white adipose tissue-specific genes was increased in VWAT of model hamsters...
  13. Gould R, Aziz H, Woods C, Seman Senderos M, Sparks E, Preuss C, et al. ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nat Genet. 2019;51:42-50 pubmed publisher
    ..Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA5-8, impeding mechanistic insight ..
  14. Tsubakihara Y, Hikita A, Yamamoto S, Matsushita S, Matsushita N, Oshima Y, et al. Arkadia enhances BMP signalling through ubiquitylation and degradation of Smad6. J Biochem. 2015;158:61-71 pubmed publisher
    ..Furthermore, we showed that Smad6, a BMP-specific inhibitory Smad, is a target of Arkadia: wild-type (WT) Arkadia, but not the C937A (CA) mutant ..
  15. Li X, Lim J, Lu J, Pedego T, Demer L, Tintut Y. Protective Role of Smad6 in Inflammation-Induced Valvular Cell Calcification. J Cell Biochem. 2015;116:2354-64 pubmed publisher
    ..Evidence suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6 and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD...
  16. Di Sanzo M, Chirillo R, Aversa I, Biamonte F, Santamaria G, Giovannone E, et al. shRNA targeting of ferritin heavy chain activates H19/miR-675 axis in K562 cells. Gene. 2018;657:92-99 pubmed publisher
    ..H19, miR-675, miR-107, Twist1, ID3, EPHB6, GNS, ANK1 and SMAD6 mRNA amounts were quantified by Taqman assay and qPCR analysis...
  17. Kotani M, Matsuda M, Murakami A, Takahashi I, Katagiri T, Hirata M. Involvement of PRIP (Phospholipase C-Related But Catalytically Inactive Protein) in BMP-Induced Smad Signaling in Osteoblast Differentiation. J Cell Biochem. 2015;116:2814-23 pubmed publisher
    ..type cells, but not in mutant cells, by pretreatment with DB867, an inhibitor of methyltransferase of inhibitory Smad6. Furthermore, BMP-induced translocation of Smad6 from nucleus to cytosol was not much observed in PRIP-deficient ..
  18. Kuratomi G, Komuro A, Goto K, Shinozaki M, Miyazawa K, Miyazono K, et al. 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 receptor. Biochem J. 2005;386:461-70 pubmed
  19. Wang C, Xia C, Bian W, Liu L, Lin W, Chen Y, et al. Cell aggregation-induced FGF8 elevation is essential for P19 cell neural differentiation. Mol Biol Cell. 2006;17:3075-84 pubmed
    ..Blocking the bone morphogenetic protein (BMP) pathway by overexpressing Smad6 in P19 cells, we also show that FGF signaling plays a BMP inhibition-independent role in P19 cell neural ..
  20. Hoover L, Kubalak S. Holding their own: the noncanonical roles of Smad proteins. Sci Signal. 2008;1:pe48 pubmed publisher
    ..Investigating these interactions will likely yield more evidence that Smads serve important and diverse purposes beyond their original reported function as signal transducers in the TGF-beta pathway. ..
  21. Martin Lopez M, Maeso Alonso L, Fuertes Alvarez S, Balboa D, Rodríguez Cortez V, Weltner J, et al. p73 is required for appropriate BMP-induced mesenchymal-to-epithelial transition during somatic cell reprogramming. Cell Death Dis. 2017;8:e3034 pubmed publisher
    ..We report that p73 is a positive modulator of the BMP circuit, enhancing its activation by DNp73 repression of the Smad6 promoter...
  22. Belus M, Rogers M, Elzubeir A, Josey M, Rose S, Andreeva V, et al. Kir2.1 is important for efficient BMP signaling in mammalian face development. Dev Biol. 2018;444 Suppl 1:S297-S307 pubmed publisher
    ..1 reduces the efficacy of BMP signaling as shown by the reduction of phosphorylated Smad 1/5/8 and reduced expression of BMP targets Smad6 and Satb2.
  23. Nitschke Y, Rutsch F. Modulators of networks: molecular targets of arterial calcification identified in man and mice. Curr Pharm Des. 2014;20:5839-52 pubmed
    ..Furthermore, intracellular signaling molecules, including SMAD6 and a number of systemic circulatory inhibitors of arterial calcification, including fetuin, tumor necrosis factor ..
  24. Leisegang M, Fork C, Josipovic I, Richter F, Preussner J, Hu J, et al. Long Noncoding RNA MANTIS Facilitates Endothelial Angiogenic Function. Circulation. 2017;136:65-79 pubmed publisher
    ..Thereby, the transcription of key endothelial genes such as SOX18, SMAD6, and COUP-TFII was regulated by ensuring efficient RNA polymerase II machinery binding...
  25. Yang D, Ma M, Zhou W, Yang B, Xiao C. Inhibition of miR-32 activity promoted EMT induced by PM2.5 exposure through the modulation of the Smad1-mediated signaling pathways in lung cancer cells. Chemosphere. 2017;184:289-298 pubmed publisher
    ..member 1 (Smad1)-mediated signaling pathway and downregulated the expression of the inhibitory Smad proteins Smad6 and Smad7 in lung cancer cells. Moreover, the knockdown of Smad1 suppressed the EMT process induced by PM2...
  26. Niu H, Liu C. The aberrant expression of Smad6 and TGF-β in obesity linked cardiac disease. Eur Rev Med Pharmacol Sci. 2017;21:138-142 pubmed
    ..In the present studies, we analyzed the expression pattern of Smad6 and TGF-β using obesity-induced mice model which are ob/ob-/- deficient...
  27. Kinsella S, Fichtner M, Watters O, König H, Prehn J. Increased A20-E3 ubiquitin ligase interactions in bid-deficient glia attenuate TLR3- and TLR4-induced inflammation. J Neuroinflammation. 2018;15:130 pubmed publisher
    ..Interactions between the de-ubiquitinating Smad6-A20 and the E3 ubiquitin ligases, TRAF3 and TRAF6, were determined by FLAG pull-down in TRAF6-FLAG or Smad6-FLAG ..
  28. Sandusky G, Berg D, Richardson M, Myers L, Grinnell B. Modulation of thrombomodulin-dependent activation of human protein C through differential expression of endothelial Smads. J Biol Chem. 2002;277:49815-9 pubmed
    ..In contrast, the opposite expression pattern was observed for Smad7. Overall, our results suggest that the relative balance of these intracellular Smads modulate the balance of endothelial function with regard to protein C activation. ..
  29. Shukla S, Sikder K, Sarkar A, Addya S, Rafiq K. Molecular network, pathway, and functional analysis of time-dependent gene changes related to cathepsin G exposure in neonatal rat cardiomyocytes. Gene. 2018;: pubmed publisher
    ..The top up-regulated genes included Hamp, SMAD6, NR4A1, FOSL2, ID3 and SLAMF7, and down-regulated genes included CYR61, GDF6, Olr640, Vom2r36, DUSP6 and MMP20...
  30. Scollen S, Luccarini C, Baynes C, Driver K, Humphreys M, Garcia Closas M, et al. TGF-β signaling pathway and breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev. 2011;20:1112-9 pubmed publisher
    ..LTBP1, LTBP2, LTBP4, TGFB1, TGFB2, TGFB3, TGFBR1(ALK5), ALK1, TGFBR2, Endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, and SMAD7 [Approved Human Gene Nomenclature Committee gene names: ACVRL1 (for ALK1) and ENG (for Endoglin)]...
  31. Katsuno Y, Qin J, Oses Prieto J, Wang H, Jackson Weaver O, Zhang T, et al. Arginine methylation of SMAD7 by PRMT1 in TGF-β-induced epithelial-mesenchymal transition and epithelial stem-cell generation. J Biol Chem. 2018;293:13059-13072 pubmed publisher
    ..TGF-β-induced SMAD3 activation is inhibited by SMAD7 and to a lesser extent by SMAD6, and SMAD6 and SMAD7 both inhibit SMAD1 and SMAD5 activation in response to the TGF-β-related bone morphogenetic ..
  32. Bianchi E, Boekelheide K, Sigman M, Lamb D, Hall S, Hwang K. Ghrelin Inhibits Post-Operative Adhesions via Blockage of the TGF-β Signaling Pathway. PLoS ONE. 2016;11:e0153968 pubmed publisher
    ..The up-regulation of inhibitory proteins Smad6 and Smad7 confirmed the ghrelin-induced blockage of TGF-β signaling...
  33. Lee N, Kirkbride K, Sheu R, Blobe G. The transforming growth factor-beta type III receptor mediates distinct subcellular trafficking and downstream signaling of activin-like kinase (ALK)3 and ALK6 receptors. Mol Biol Cell. 2009;20:4362-70 pubmed publisher
    ..stimulation of the BMP-responsive promoters XVent2 and 3GC2, and up-regulation of the early response gene Smad6. In contrast, TbetaRIII specifically enhanced ALK3-mediated up-regulation of the early response gene ID-1...
  34. Kirkpatrick B, Morris C. A Major Gene for Bovine Ovulation Rate. PLoS ONE. 2015;10:e0129025 pubmed publisher
    ..This region contains three candidate genes, SMAD3, SMAD6 and IQCH...
  35. Wylie L, Mouillesseaux K, Chong D, Bautch V. Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted endothelial cell junctions. Dev Biol. 2018;442:199-209 pubmed publisher
    ..Recently, we showed that SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases vessel sprouting and branching both in ..
  36. Chen Z, Lu X, Jia D, Jing Y, Chen D, Wang Q, et al. Hepatic SMARCA4 predicts HCC recurrence and promotes tumour cell proliferation by regulating SMAD6 expression. Cell Death Dis. 2018;9:59 pubmed publisher
    ..Finally, we discovered that one of the mechanisms by which BRG1 promotes cell proliferation is the upregulation of SMAD6. These findings highlight the important role of BRG1 in the regulation of HCC proliferation and provide valuable ..
  37. Xu S, Wu X. miR-134 inhibits chondrogenic differentiation of bone marrow mesenchymal stem cells by targetting SMAD6. Biosci Rep. 2019;39: pubmed publisher
    ..Subsequently, the correlation between miR-134 and SMAD6 was assessed via bioinformatics analysis and dual-luciferase reporter assay...
  38. Zhang J, Zhang L, Cui H, Zhang X, Zhang G, Yang X, et al. High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy. Cancer Gene Ther. 2018;: pubmed publisher
    ..05) in AML patients undergoing chemotherapy; and high SMAD6 expression was associated with shorter EFS and OS (all P < 0.01) in patients underwent allo-HSCT...
  39. Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, et al. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003;22:6458-70 pubmed
    ..Arkadia may thus play an important role as an amplifier of TGF-beta superfamily signalling under both physiological and pathological conditions. ..
  40. Iwata N, Hasegawa T, Fujita S, Nagao S, Nakano Y, Nada T, et al. Effect of the interaction of metformin and bone morphogenetic proteins on ovarian steroidogenesis by human granulosa cells. Biochem Biophys Res Commun. 2018;503:1422-1427 pubmed publisher
    ..Moreover, metformin treatment increased the expression of inhibitory Smad6, but not of that Smad7, in human granulosa cells, while metformin had no significant impact on the expression ..
  41. Sangadala S, Metpally R, Reddy B. Molecular interaction between Smurf1 WW2 domain and PPXY motifs of Smad1, Smad5, and Smad6--modeling and analysis. J Biomol Struct Dyn. 2007;25:11-23 pubmed
    ..We carried out docking of Smurf1 WW2 domain with the PPXY motifs of Smad1, Smad5, and Smad6 and identified the key amino acid residues involved in interaction...
  42. Birkou M, Chasapis C, Marousis K, Loutsidou A, Bentrop D, Lelli M, et al. A Residue Specific Insight into the Arkadia E3 Ubiquitin Ligase Activity and Conformational Plasticity. J Mol Biol. 2017;429:2373-2386 pubmed publisher
    ..factor beta (TGF-β) signaling responses by targeting for degradation the negative regulators of the pathway, Smad6 and Smad7, and the nuclear co-repressors Ski and Skil (SnoN)...
  43. Janin A, Bauer D, Ratti F, Valla C, Bertrand A, Christin E, et al. SMAD6 overexpression leads to accelerated myogenic differentiation of LMNA mutated cells. Sci Rep. 2018;8:5618 pubmed publisher
    ..we identified two major alterations in the BMP (Bone Morphogenetic Protein) pathway: Bmp4 downregulation and Smad6 overexpression...
  44. Lin X, Liang Y, Sun B, Liang M, Shi Y, Brunicardi F, et al. Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription. Mol Cell Biol. 2003;23:9081-93 pubmed
    b>Smad6 and Smad7 are inhibitory Smads induced by transforming growth factor beta-Smad signal transduction pathways in a negative-feedback mechanism...
  45. Ichijo T, Voutetakis A, Cotrim A, Bhattachryya N, Fujii M, Chrousos G, et al. The Smad6-histone deacetylase 3 complex silences the transcriptional activity of the glucocorticoid receptor: potential clinical implications. J Biol Chem. 2005;280:42067-77 pubmed
    ..b>Smad6, one of the transforming growth factor beta (TGFbeta) family downstream transcription factors, interacts with the ..
  46. Lee Y, Park J, Jung S, Kim S, Kim J, Lee J, et al. Inhibition of lethal inflammatory responses through the targeting of membrane-associated Toll-like receptor 4 signaling complexes with a Smad6-derived peptide. EMBO Mol Med. 2015;7:577-92 pubmed publisher
    We have previously reported that Smad6, one of the inhibitory Smads of transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signaling, inhibits Toll-like receptor (TLR) 4 signaling by disrupting the Pellino-1-..
  47. Schweighofer N, Aigelsreiter A, Trummer O, Graf Rechberger M, Hacker N, Kniepeiss D, et al. Direct comparison of regulators of calcification between bone and vessels in humans. Bone. 2016;88:31-38 pubmed publisher
    ..receptor activator of NF-?B ligand (RANKL), osteopontin (OPN), matrix gla protein (MGP), bone sialoprotein (BSP), SMAD6, and runt-related transcription factor 2 (RUNX2) were determined in bone, aorta, and external iliac artery tissue ..
  48. Jiao J, Zhang R, Li Z, Yin Y, Fang X, Ding X, et al. Nuclear Smad6 promotes gliomagenesis by negatively regulating PIAS3-mediated STAT3 inhibition. Nat Commun. 2018;9:2504 pubmed publisher
    ..In this study, we report that Smad6 is overexpressed in nuclei of glioma cells, which correlates with poor patient survival and regulates STAT3 ..
  49. Araújo V, Silva G, Duarte A, Magalhães Padilha D, Almeida A, Lunardi F, et al. Bone Morphogenetic Protein-6 (BMP-6) Stimulates the Antrum Formation by the Regulation of its Signalling Pathway in Caprine Pre-antral Follicles Cultured In Vitro. Reprod Domest Anim. 2016;51:59-68 pubmed publisher
    ..Experiment 1) and the mRNA levels for BMP receptors/Smad signalling pathway (BMPR1A, BMPR2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7 and SMAD8) in vivo and in vitro using BMP-6 (Experiment 2)...
  50. Faherty N, Benson M, Sharma E, Lee A, Howarth A, Lockstone H, et al. Negative autoregulation of BMP dependent transcription by SIN3B splicing reveals a role for RBM39. Sci Rep. 2016;6:28210 pubmed publisher
    BMP signalling is negatively autoregulated by several genes including SMAD6, Noggin and Gremlin, and autoregulators are possible targets for enhancing BMP signalling in disorders such as fibrosis and pulmonary hypertension...
  51. Li Q, Wu H, Chen B, Hu G, Huang L, Qin K, et al. SNPs in the TGF-? signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer. PLoS ONE. 2012;7:e51713 pubmed publisher
    ..Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain ..
  52. Kaiser M, Haag J, Soder S, Bau B, Aigner T. Bone morphogenetic protein and transforming growth factor beta inhibitory Smads 6 and 7 are expressed in human adult normal and osteoarthritic cartilage in vivo and are differentially regulated in vitro by interleukin-1beta. Arthritis Rheum. 2004;50:3535-40 pubmed
    ..In this study, we investigated whether intracellular inhibitors of BMP and TGFbeta signaling, inhibitory Smad6 (I-Smad6) and I-Smad7, are expressed in articular chondrocytes in normal and osteoarthritic (OA) cartilage, and ..
  53. Ha Thi H, Kim H, Choi S, Kang J, Kim S, Hong S. Smad7 Modulates Epidermal Growth Factor Receptor Turnover through Sequestration of c-Cbl. Mol Cell Biol. 2015;35:2841-50 pubmed publisher
    ..Interestingly, wild-type Smad7, but not Smad6 or mutant Smad7, destabilized the EGF-induced complex formation of c-Cbl and EGFR...
  54. Caldwell R, Gadipatti R, Lane K, Shepherd V. HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in U937 monocytic cells. J Leukoc Biol. 2006;79:192-201 pubmed
    ..Similar to mothers against decapentaplegics (SMAD) phosphorylation and SMAD6 expression, in response to BMP2 treatment, were down-regulated after Tat treatment...
  55. Lin H, Ying Y, Wang Y, Wang G, Jiang S, Huang D, et al. AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation. Biochim Biophys Acta Mol Cell Res. 2017;1864:2369-2377 pubmed publisher
    ..Furthermore, activation of AMPK upregulated Smad6 and Smurf1 and thereby enhanced their interactions, resulting in its proteosome-dependent degradation of ALK2...
  56. Rautava S, Nanthakumar N, Dubert Ferrandon A, Lu L, Rautava J, Walker W. Breast milk-transforming growth factor-?? specifically attenuates IL-1?-induced inflammatory responses in the immature human intestine via an SMAD6- and ERK-dependent mechanism. Neonatology. 2011;99:192-201 pubmed publisher
    ..b>SMAD6 knockdown was performed by transfecting the cells with SMAD6 siRNA...
  57. Katsuyama T, Otsuka F, Terasaka T, Inagaki K, Takano Narazaki M, Matsumoto Y, et al. Regulatory effects of fibroblast growth factor-8 and tumor necrosis factor-α on osteoblast marker expression induced by bone morphogenetic protein-2. Peptides. 2015;73:88-94 pubmed publisher
    ..influence on the expression levels of TNF receptors, while FGF-8 suppressed the expression of inhibitory Smad6 and Smad7, suggesting a possible feedback activity through FGF to BMP receptor (BMPR) signaling...
  58. Zhou Q, Heinke J, Vargas A, Winnik S, Krauss T, Bode C, et al. ERK signaling is a central regulator for BMP-4 dependent capillary sprouting. Cardiovasc Res. 2007;76:390-9 pubmed
    ..On the other hand, stimulation of Smad 6 inhibits ERK activation and thus results in a negative feedback loop to fine-tune BMP signaling in HUVECs. ..
  59. Wrana J, Attisano L. The Smad pathway. Cytokine Growth Factor Rev. 2000;11:5-13 pubmed
    ..In addition, we will summarize recent findings on the role of Smads as transcriptional co-modulators. ..
  60. Banka S, Cain S, Carim S, Daly S, Urquhart J, Erdem G, et al. Leri's pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into systemic sclerosis pathogenesis. Ann Rheum Dis. 2015;74:1249-56 pubmed publisher
    ..Western blot analysis revealed markedly decreased inhibitory SMAD6 levels in patients with LP...
  61. Xu H, Liu C, Sun Z, Guo X, Zhang Y, Liu M, et al. CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis. Int J Mol Med. 2015;36:123-9 pubmed publisher
    ..Additionally, CCN5 over-expression decreased CCN2 expression and increased Smad6 phosphorylation...
  62. Yan X, Liao H, Cheng M, Shi X, Lin X, Feng X, et al. Smad7 Protein Interacts with Receptor-regulated Smads (R-Smads) to Inhibit Transforming Growth Factor-β (TGF-β)/Smad Signaling. J Biol Chem. 2016;291:382-92 pubmed publisher
    ..These results shed new light on the regulation of TGF-β signaling by Smad7. ..
  63. Li Q. Inhibitory SMADs: potential regulators of ovarian function. Biol Reprod. 2015;92:50 pubmed publisher
    ..components consisting of receptor-regulated SMADs (SMAD1/2/3/5/9), a common SMAD (SMAD4), and inhibitory SMADs (SMAD6/7)...
  64. Stantzou A, Schirwis E, Swist S, Alonso Martin S, Polydorou I, Zarrouki F, et al. BMP signaling regulates satellite cell-dependent postnatal muscle growth. Development. 2017;144:2737-2747 pubmed publisher
    ..knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth...
  65. Wang Y, Wu J, Lin B, Li X, Zhang H, Ding H, et al. Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway. Toxicology. 2014;326:9-17 pubmed publisher
    ..pathway and increased TGF-β receptor I (RI), TGF-βRII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Smad6 and Smad7 levels...
  66. Frullanti E, Colombo F, Falvella F, Galvan A, Noci S, De Cecco L, et al. Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue. Int J Cancer. 2012;131:E643-8 pubmed publisher
    ..Studies in vitro indicated that four of the genes (SLC14A1, SMAD6, TMEM100 and TXNIP) inhibited colony formation of lung cancer cell lines transfected to overexpress the genes, ..
  67. Zheng S, Long J, Liu Z, Tao W, Wang D. Identification and Evolution of TGF-? Signaling Pathway Members in Twenty-Four Animal Species and Expression in Tilapia. Int J Mol Sci. 2018;19: pubmed publisher
    ..Duplications of TGFB2, TGFBR2, ACVR1, SMAD4 and SMAD6, which were resulted from 2R, were first isolated...
  68. Graef J, Rendina Ruedy E, Crockett E, Ouyang P, King J, Cichewicz R, et al. Select polyphenolic fractions from dried plum enhance osteoblast activity through BMP-2 signaling. J Nutr Biochem. 2018;55:59-67 pubmed publisher
    ..0674). This response coincided with suppressed gene expression of Bmp2 and the up-regulation of Smad6, an inhibitor of BMP signaling. DP-FrA and DP-FrB partially normalized these responses...
  69. Tsunobuchi H, Ishisaki A, Imamura T. Expressions of inhibitory Smads, Smad6 and Smad7, are differentially regulated by TPA in human lung fibroblast cells. Biochem Biophys Res Commun. 2004;316:712-9 pubmed
    b>Smad6 and Smad7 are inhibitory Smads (I-Smads) with differential inhibitory effects on the regulation of the cellular signalings induced by TGF-beta superfamily...
  70. Hayashi Y, Hsiao E, Sami S, Lancero M, Schlieve C, Nguyen T, et al. BMP-SMAD-ID promotes reprogramming to pluripotency by inhibiting p16/INK4A-dependent senescence. Proc Natl Acad Sci U S A. 2016;113:13057-13062 pubmed
    ..was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7)...
  71. Gu H, Xu J, Huang Z, Wu L, Zhou K, Zhang Y, et al. Identification and differential expression of microRNAs in 1, 25-dihydroxyvitamin D3-induced osteogenic differentiation of human adipose-derived mesenchymal stem cells. Am J Transl Res. 2017;9:4856-4871 pubmed
    ..osteoblast differentiation, were confirmed to be significantly up-regulated in VD3-induced cells by qRT-PCR; while Smad6 and activinRI, which are negative regulators of the TGF-?/BMP superfamily, were shown to be significantly down-..
  72. Seet L, Toh L, Finger S, Chu S, Stefanovic B, Wong T. Valproic acid suppresses collagen by selective regulation of Smads in conjunctival fibrosis. J Mol Med (Berl). 2016;94:321-34 pubmed publisher
    ..Moreover, VPA decreased Smad2, Smad3 and Smad4 but increased Smad6 expression with a similar intensity-exposure profile...
  73. Cesarz Z, Funnell J, Guan J, Tamama K. Soft Elasticity-Associated Signaling and Bone Morphogenic Protein 2 Are Key Regulators of Mesenchymal Stem Cell Spheroidal Aggregates. Stem Cells Dev. 2016;25:622-35 pubmed publisher
    ..Contrary to expectations, BMP2 signaling decreased expression of IL1B and downstream genes in a SMAD6-dependent manner. Conversely, IL1B signaling enhanced BMP2 expression...
  74. Lu X, Yao X, Yan C, Wan Q, Li Y. Functional role of NKX2-5 and Smad6 expression in developing rheumatic heart disease. Eur Rev Med Pharmacol Sci. 2016;20:715-20 pubmed
    ..The present investigation of NKX2-5 and Smad-6 in RHD provides a new insight of data that helps to understand the disease pathogenesis. ..
  75. Lelieveld S, Reijnders M, Pfundt R, Yntema H, Kamsteeg E, de Vries P, et al. Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Nat Neurosci. 2016;19:1194-6 pubmed publisher
    ..Statistical analyses identified 10 new candidate ID genes: DLG4, PPM1D, RAC1, SMAD6, SON, SOX5, SYNCRIP, TCF20, TLK2 and TRIP12...
  76. Shi W, Wang H, Zheng X, Jiang X, Xu Z, Shen H, et al. HNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells. Biol Trace Elem Res. 2017;176:294-304 pubmed publisher
    ..Neither inhibitory SMADs, SMAD6, and SMAD7 nor BMPR ligands, BMP2, BMP4, BMP6, and BMP7 were regulated by HNF-4? in HepG2 cells...
  77. Priyadarsini S, McKay T, Sarker Nag A, Karamichos D. Keratoconus in vitro and the key players of the TGF-β pathway. Mol Vis. 2015;21:577-88 pubmed
    ..We found a significant downregulation in the SMAD6 and SMAD7 expressions by HKCs when compared to HCFs (p≤0.05)...
  78. Tseng Z, Vittinghoff E, Musone S, Lin F, Whiteman D, Pawlikowska L, et al. Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease. Heart Rhythm. 2009;6:1745-50 pubmed publisher
    ..Nineteen SNPs among 5 genes (TGFB2, TGFBR2, SMAD1, SMAD3, SMAD6) were associated with SCA after adjustment for age and sex...
  79. Fang H, Song P, Shen C, Liu X, Li H. Bone mesenchymal stem cell-conditioned medium induces the upregulation of Smad6, which inhibits the BMP-4/Smad1/5/8 signaling pathway. Neurol Res. 2016;38:965-972 pubmed
    ..acidic protein (GFAP) and BMP receptors (BMPRII and BMPRIa) was determined by western blot, while SMAD1/5/8 and SMAD6 mRNA expression was detected by quantitative real-time polymerase chain reaction (Q-RT-PCR)...
  80. Mouillesseaux K, Wiley D, Saunders L, Wylie L, Kushner E, Chong D, et al. Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6. Nat Commun. 2016;7:13247 pubmed publisher
    ..ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression...
  81. Fujita S, Hasegawa T, Nishiyama Y, Fujisawa S, Nakano Y, Nada T, et al. Interaction between orexin A and bone morphogenetic protein system on progesterone biosynthesis by rat granulosa cells. J Steroid Biochem Mol Biol. 2018;181:73-79 pubmed publisher
    ..orexin A suppressed the mRNA expression of both type-I and -II receptors for BMPs and increased that of inhibitory Smad6 and Smad7 in granulosa cells...
  82. Konrad L, Scheiber J, Bergmann M, Eickelberg O, Hofmann R. Identification of a new human Smad6 splice variant. Andrologia. 2008;40:358-63 pubmed publisher
    b>Smad6 and Smad7 are inhibitory Smad proteins, which are essential in the negative regulation of BMP and TGF-beta/activin-signalling...
  83. Ryan J, Ryan E, Fabre A, Lawless M, Crowe J. Defective bone morphogenic protein signaling underlies hepcidin deficiency in HFE hereditary hemochromatosis. Hepatology. 2010;52:1266-73 pubmed publisher
    ..Furthermore, Smad6 and Smad7, inhibitors of BMP signaling, were up-regulated in HFE-HH compared to controls (P = 0.001 and P = 0...
  84. Kang Y, Shin J, Yoon J, Oh I, Lee S, Kim S, et al. Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stem cells. Biochem Biophys Res Commun. 2012;423:750-6 pubmed publisher
    ..However, roles of Smad6 in hematopoiesis remained unknown in contrast to the other inhibitory Smad (I-Smad), Smad7...
  85. Zhang X, Zhang J, Bauer A, Zhang L, Selinger D, Lu C, et al. Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. EMBO J. 2013;32:996-1007 pubmed publisher
    b>SMAD6 is a crucial feedback inhibitory regulator of bone morphogenetic protein (BMP)/SMAD signalling...
  86. Toma K, Otsuka F, Oguni K, Terasaka T, Komatsubara M, Tsukamoto Yamauchi N, et al. BMP-6 modulates somatostatin effects on luteinizing hormone production by gonadrotrope cells. Peptides. 2016;76:96-101 pubmed publisher
    ..Somatostatin analogs also impaired BMP-6-induced Smad1/5/8 phosphorylation by suppressing BMPRs and augmenting Smad6/7 expression...
  87. Zhang F, Sodroski C, Cha H, Li Q, Liang T. Infection of Hepatocytes With HCV Increases Cell Surface Levels of Heparan Sulfate Proteoglycans, Uptake of Cholesterol and Lipoprotein, and Virus Entry by Up-regulating SMAD6 and SMAD7. Gastroenterology. 2017;152:257-270.e7 pubmed publisher
    The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor β signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV)...
  88. Morén A, Imamura T, Miyazono K, Heldin C, Moustakas A. Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J Biol Chem. 2005;280:22115-23 pubmed
    ..E3 ligases, via formation of ternary complexes between Smad4 and Smurfs, mediated by R-Smads (Smad2) or I-Smads (Smad6/7), acting as adaptors...
  89. Wang Z, Nakamura K, Jinnin M, Kudo H, Goto M, Era T, et al. Establishment and gene expression analysis of disease-derived induced pluripotent stem cells of scleroderma. J Dermatol Sci. 2016;84:186-196 pubmed publisher
    ..normal iPSC (NS-iPSC) and SSc-iPSC by PCR array, and found constitutive and significant down-regulation of S100A8, Smad6, and TGF-?2 in SSc-iPSC...
  90. García E, Hamdi M, Barrera A, Sánchez Calabuig M, Gutiérrez Adán A, Rizos D. Bovine embryo-oviduct interaction in vitro reveals an early cross talk mediated by BMP signaling. Reproduction. 2017;153:631-643 pubmed publisher
    ..of the period, significantly reduced the relative abundance of BMPR1B, BMPR2, SMAD1, SMAD6 and ID2 mRNAs in BOEC...
  91. Riggins G, Thiagalingam S, Rozenblum E, Weinstein C, Kern S, Hamilton S, et al. Mad-related genes in the human. Nat Genet. 1996;13:347-9 pubmed
    ..These data suggest that this gene family may prove to be important in the suppression of neoplasia, imparting the growth inhibitory effects of TGF-beta-like ligands. ..
  92. Shintani M, Yagi H, Nakayama T, Saji T, Matsuoka R. A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. J Med Genet. 2009;46:331-7 pubmed publisher
    ..We screened for mutations in ENDOGLIN(ENG), SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6 and SMAD8 genes, which are involved in the TGF-beta/BMP signallings, in 23 patients with IPAH who had no mutations ..