IndraLab

"The use of Smad7 to block Smad3 effects differs from studies utilizing Smad3 knock-out mice as Smad7 would inhibit both Smad2 and 3 whereas Smad3 knock-out mice, on the other hand, are a selective and complete loss of Smad3."

"Overexpression of Smad7 inhibits both Smad3 mediated renal fibrosis and NF-kappaB-driven renal inflammation."

"Inhibition of Smad7 with a specific antisense oligonucleotide restores TGF-beta1 and Smad3 signaling, resulting in a marked suppression of inflammatory cytokine production."

"While Smad7 represses Smad3 activation by TGF-beta, it does not reverse the inhibitory effect of TGF-beta on myogenesis, suggesting a different function in myogenic cells."

"Whereas SMAD7 inhibits both TGF-beta and SMAD3 and BMP and SMAD1 signaling, SMAD6 is a relatively specific inhibitor of BMP signaling."

"Smad7 was recently shown to antagonize TGF-beta-induced activation of signal transducing Smad2 and Smad3 proteins."

"Similar results were evident following induction of the intracellular Smad2 and Smad3 antagonist Smad7 by hepatocyte growth factor in RLE-6TN cells [XREF_BIBR]."

"Smad7, a negative feedback inhibitor, can block Smad2 and Smad3 access to TGF-beta receptor 1."

"Furthermore, in RA, not only did the inhibition of Smad7 promote TGFbeta and Smad3 signalling and tissue fibrosis, but it also markedly enhanced NF-kappaB-driven inflammation [XREF_BIBR]."

"Overexpression of Smad7 not only inhibits Smad3 mediated renal fibrosis such as collagen matrix expression including epithelial-mesenchymal transition, but also blocks NF-kappaB-driven renal inflammation including accumulation of macrophages and T cells in both glomeruli and tubulointerstitium and upregulation of renal IL-1, TNFalpha, ICAM-1, and iNOS."

"Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-beta signaling in podocytes"

"Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-beta signaling in podocytes"

"Smad7 was recently shown to antagonize TGF-beta-induced activation of signal-transducing Smad2 and Smad3 proteins"

"Smad7 was recently shown to antagonize TGF-beta-induced activation of signal-transducing Smad2 and Smad3 proteins"

"Smad7 interacts with activated TbetaRI to prevent the activation of Smad2 and Smad3 (R-Smads), thus, interrupting ligand induced signaling."

"Simplified schematic drawing of the TGF-?-Smad pathway. Binding of TGF-? to its type II receptor in concert with the type I receptor (A) leads to formation of a receptor complex and phosphorylation of the type I receptor. The type I receptor subsequently phosphorylates Smad2 or 3 (B), allowing this complex to associate with Smad4 and move into the nucleus (C). In the nucleus, the Smad complex associates with a transcription factor and this complex binds to specific enhancers in target genes (down-) regulating transcription (D). TNF is able to interfere with TGF-? signaling through the upregulation of the inhibitory Smad7 protein (E). Smad7 is capable of inhibiting the Smad2 and 3 phosphorylating process by competing with the receptor interaction but Smad7 also can dephosphorylate the complex. In addition, Smad7 itself is capable to upregulate TGF? gene expression. As described in the discussion, CSE is most likely capable to interfere with the Smad pathway although this is not yet fully elucidated. (F). Phosphorylated Smad3 is able to stimulate the transcription of the decorin gene (G)."

"The activated TGF-beta R1 phosphorylates SMAD2 and SMAD3, which bind to the SMAD4 mediator to move into the nucleus and form complexes that regulate transcription."