Gene Symbol: Smad5
Description: SMAD family member 5
Alias: Madh5, mothers against decapentaplegic homolog 5, MAD homolog 5, SMAD 5, SMAD, mothers against DPP homolog 5, mothers against DPP homolog 5
Species: rat
Products:     Smad5

Top Publications

  1. Korchynskyi O, Ten Dijke P. Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J Biol Chem. 2002;277:4883-91 pubmed
    ..Our results provide important new insights into how the BMP/Smad pathway can specifically activate target genes. ..
  2. Pangas S, Li X, Umans L, Zwijsen A, Huylebroeck D, Gutierrez C, et al. Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol. 2008;28:248-57 pubmed
    ..Single conditional knockouts for Smad1 or Smad5 or mice homozygous null for Smad8 are viable and fertile...
  3. Ji S, Jaffrey S. Intra-axonal translation of SMAD1/5/8 mediates retrograde regulation of trigeminal ganglia subtype specification. Neuron. 2012;74:95-107 pubmed publisher
    ..Thus, local translation functions as a mechanism by which coincident signals are converted into a retrograde signal that elicits a specific transcriptional response. ..
  4. Visser J, Olaso R, Verhoef Post M, Kramer P, Themmen A, Ingraham H. The serine/threonine transmembrane receptor ALK2 mediates Müllerian inhibiting substance signaling. Mol Endocrinol. 2001;15:936-45 pubmed
    ..The use of this ubiquitously expressed type I receptor underscores the role of the MIS ligand and the MIS type II receptor in establishing the specificity of the MIS signaling cascade. ..
  5. Takahashi H, Goto N, Kojima Y, Tsuda Y, Morio Y, Muramatsu M, et al. Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2006;290:L450-8 pubmed
    ..These results suggest abrogation of BMP signaling may be a common molecular pathogenesis in the development of PH with various pathophysiological events, including primary and hypoxic PH. ..
  6. Anhê F, Lellis Santos C, Leite A, Hirabara S, Boschero A, Curi R, et al. Smad5 regulates Akt2 expression and insulin-induced glucose uptake in L6 myotubes. Mol Cell Endocrinol. 2010;319:30-8 pubmed publisher
    ..However, the mechanism by which BMP9 modulates insulin action remains unknown. Here we demonstrate that Smad5, a transcription factor activated by BMP9, and Akt2, are upregulated in differentiated L6 myotubes...
  7. Davis B, Hilyard A, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature. 2008;454:56-61 pubmed publisher
  8. Fukada T, Civic N, Furuichi T, Shimoda S, Mishima K, Higashiyama H, et al. The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways. PLoS ONE. 2008;3:e3642 pubmed publisher
    ..The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-beta signaling and connective tissue dysfunction. ..
  9. Tripurani S, Cook R, Eldin K, Pangas S. BMP-specific SMADs function as novel repressors of PDGFA and modulate its expression in ovarian granulosa cells and tumors. Oncogene. 2013;32:3877-85 pubmed publisher
    ..that conditional deletion of two transcription factors that signal for the bone morphogenetic proteins (Smad1 and Smad5) in ovarian granulosa cells causes metastatic granulosa cell tumors (GCTs) in female mice and phenocopies human ..

More Information


  1. Sowa H, Kaji H, Hendy G, Canaff L, Komori T, Sugimoto T, et al. Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2. J Biol Chem. 2004;279:40267-75 pubmed
    ..In osteoblasts the interaction of menin and the transforming growth factor-beta/Smad3 pathway negatively regulates the BMP-2/Smad1/5- and Runx2-induced transcriptional activities leading to inhibition of late-stage differentiation. ..
  2. Rath B, Nam J, Deschner J, Schaumburger J, Tingart M, Grassel S, et al. Biomechanical forces exert anabolic effects on osteoblasts by activation of SMAD 1/5/8 through type 1 BMP receptor. Biorheology. 2011;48:37-48 pubmed publisher
    ..Collectively, the present findings demonstrate that biomechanical stimulation of osteoblasts activates SMAD 1/5/8 in the BMP signaling pathway through BMPR1 and may enhance osteogenesis by upregulating SMAD-dependent osteogenic genes. ..
  3. Meynard D, Kautz L, Darnaud V, Canonne Hergaux F, Coppin H, Roth M. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet. 2009;41:478-81 pubmed publisher
    ..Despite their severe iron overload, the livers of Bmp6-deficient mice have low levels of phosphorylated Smad1, Smad5 and Smad8, and these Smads are not significantly translocated to the nucleus...
  4. Cho Y, Yoon W, Woo K, Baek J, Park J, Ryoo H. The canonical BMP signaling pathway plays a crucial part in stimulation of dentin sialophosphoprotein expression by BMP-2. J Biol Chem. 2010;285:36369-76 pubmed publisher
    ..Thus, the canonical BMP-2 signaling pathway plays a crucial part in the regulation of Dspp expression through the action of Smads, Dlx5, Runx2, and Msx2...
  5. Rosendahl A, Pardali E, Speletas M, Ten Dijke P, Heldin C, Sideras P. Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation. Am J Respir Cell Mol Biol. 2002;27:160-9 pubmed
  6. Caubit X, Lye C, Martin E, Coré N, Long D, Vola C, et al. Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4. Development. 2008;135:3301-10 pubmed publisher
  7. Yang J, Li X, Al Lamki R, Southwood M, Zhao J, Lever A, et al. Smad-dependent and smad-independent induction of id1 by prostacyclin analogues inhibits proliferation of pulmonary artery smooth muscle cells in vitro and in vivo. Circ Res. 2010;107:252-62 pubmed publisher
    ..Prostacyclin analogues enhance Id1 expression in vitro and in vivo and restore deficient BMP signaling in BMPR-II mutant PASMCs. ..
  8. Morty R, Nejman B, Kwapiszewska G, Hecker M, Zakrzewicz A, Kouri F, et al. Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol. 2007;27:1072-8 pubmed
    ..BMP signaling and BMP-regulated physiological phenomena are perturbed in MCT-treated rats, lending solid support to the proposed roles for BMP signaling in the pathogenesis of human PAH. ..
  9. Morikawa Y, Zehir A, Maska E, Deng C, Schneider M, Mishina Y, et al. BMP signaling regulates sympathetic nervous system development through Smad4-dependent and -independent pathways. Development. 2009;136:3575-84 pubmed publisher
  10. Umans L, Cox L, Tjwa M, Bito V, Vermeire L, Laperre K, et al. Inactivation of Smad5 in endothelial cells and smooth muscle cells demonstrates that Smad5 is required for cardiac homeostasis. Am J Pathol. 2007;170:1460-72 pubmed
    ..b>Smad5 and Smad1 are highly homologous, and they mediate primarily bone morphogenetic protein (Bmp) signals...
  11. Zhan Y, Fujino A, MacLaughlin D, Manganaro T, Szotek P, Arango N, et al. Müllerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Müllerian duct regression. Development. 2006;133:2359-69 pubmed
    ..MIS induces expression of Alk2, Alk3 and Smad8, but downregulates Smad5 in the urogenital ridge...
  12. Lenox L, Perry J, Paulson R. BMP4 and Madh5 regulate the erythroid response to acute anemia. Blood. 2005;105:2741-8 pubmed
    ..Here, we show that f/f mutant mice have a mutation in Madh5. Our analysis shows that BMP4/Madh5-dependent signaling, regulated by hypoxia, initiates the differentiation and ..
  13. Vrljicak P, Myburgh D, Ryan A, Van Rooijen M, Mummery C, Gupta I. Smad expression during kidney development. Am J Physiol Renal Physiol. 2004;286:F625-33 pubmed
    ..Based on the observed patterns of expression, we speculate that individual or combinations of Smads may play specific roles in cell-fate determination during kidney development. ..
  14. Hou F, Liu R, Liu X, Cui L, Wen Y, Yan S, et al. Attenuation of liver fibrosis by herbal compound 861 via upregulation of BMP-7/Smad signaling in the bile duct ligation model rat. Mol Med Rep. 2016;13:4335-42 pubmed publisher
    ..In comparison with the saline?treated BDL rats, Cpd 861 markedly upregulated the gene expression of BMP?7 and Smad5, as well as the protein expression of BMP?7 and Smad1/5...
  15. Wang H, Jiang Y, Lu M, Sun B, Qiao X, Xue D, et al. STX12 lncRNA/miR-148a/SMAD5 participate in the regulation of pancreatic stellate cell activation through a mechanism involving competing endogenous RNA. Pancreatology. 2017;17:237-246 pubmed publisher
    ..The expression of the interleukin 6 signal transducer (IL6ST), SMAD family member 5 (SMAD5) and alpha smooth muscle actin (?-SMA) proteins were examined by western blot...
  16. Nahar Gohad P, Gohad N, Tsai C, Bordia R, Vyavahare N. Rat aortic smooth muscle cells cultured on hydroxyapatite differentiate into osteoblast-like cells via BMP-2-SMAD-5 pathway. Calcif Tissue Int. 2015;96:359-69 pubmed publisher
    ..Blocking CaSR by NPS-2143 reduced BMP-2 secretion and blocking the BMP-2 pathway by LDN-193189, a BMP inhibitor, modulated expression of osteogenic markers confirming their role in osteogenesis of Vsmcs. ..
  17. Chen W, Xia J, Hu P, Zhou F, Chen Y, Wu J, et al. Follistatin-like 1 protects cardiomyoblasts from injury induced by sodium nitroprusside through modulating Akt and Smad1/5/9 signaling. Biochem Biophys Res Commun. 2016;469:418-23 pubmed publisher
    ..Taken together, these results indicated that FSTL1 protects the SNP-induced injury in cardiac H9c2 cells through, at least in part, the activation of Akt and inhibition of Smad1/5/9 signaling. ..
  18. Zavadil J, Brezinova J, Svoboda P, Zemanova Z, Michalova K. Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60. Leukemia. 1997;11:1187-92 pubmed
    ..1 critical locus and localized the transcriptional transactivator Smad5 adjacent to loci showing consistent loss of heterozygosity in these disorders...
  19. Zhao M, Ko S, Liu J, Chen D, Zhang J, Wang B, et al. Inhibition of microtubule assembly in osteoblasts stimulates bone morphogenetic protein 2 expression and bone formation through transcription factor Gli2. Mol Cell Biol. 2009;29:1291-305 pubmed publisher
    ..In summary, inhibition of microtubule assembly enhances BMP-2 gene transcription and subsequent bone formation, in part, through inhibiting proteasomal processing of Gli2 and increasing intracellular Gli2 concentrations. ..
  20. Liu C, Chang E, Yu J, Carlson C, Prazak L, Yu X, et al. The interferon-inducible p204 protein acts as a transcriptional coactivator of Cbfa1 and enhances osteoblast differentiation. J Biol Chem. 2005;280:2788-96 pubmed
    ..p204, which is the first interferon-inducible protein found to associate with Cbfa1, functions as a novel regulator of osteoblast differentiation. ..
  21. Yu Y, Yang J, Chapman Sheath P, Walsh W. TGF-beta, BMPS, and their signal transducing mediators, Smads, in rat fracture healing. J Biomed Mater Res. 2002;60:392-7 pubmed
    ..At day 10, Smad6 increased dramatically, Smad2, Smad3, and Smad4 remained elevated while Smad1 and Smad5 decreased in the fracture callus. Smad7 was expressed only in vascular endothelial cells...
  22. Chang H, Matzuk M. Smad5 is required for mouse primordial germ cell development. Mech Dev. 2001;104:61-7 pubmed
    b>Smad5, together with Smad1 and Smad8, have been implicated as downstream signal mediators for several bone morphogenetic proteins (BMPs)...
  23. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001;276:12477-80 pubmed
    ..These results thus reveal a novel function of Smad7, i.e. induction of degradation of TbetaR-I through recruitment of an E3 ligase to the receptor. ..