Here, we review and discuss the available evidence about the role of TGF-β1 and Smad7, an inhibitor of TGF-β1 activity, in gut inflammation, fibrosis and cancer with particular regard to the contribution of these two molecules in the pathogenesis of inflammatory bowel …

Oct 9, 1997 · Transfection of Smad7 blocks responses mediated by TGF-β in mammalian cells, and injection of Smad7 RNA into Xenopus embryos blocks activin/TGF-β signalling. Smad7 associates stably with the...

These results show that Smad7 blockade of TGF-β1 signaling helps maintain the chronic production of proinflammatory cytokines that drives the inflammatory process in IBD and that inhibition of Smad7 enables endogenous TGF-β to downregulate this response.

Aug 1, 2002 · Smad7 is a major inhibitory regulator of transforming growth factor (TGF)-β signaling. Smad7 expression is induced by TGF-β itself and other signaling pathways, indicating a key role for Smad7 in feedback or cross-talk control of TGF-β signaling.

Aug 23, 2023 · The importance of Smad7 in negatively regulating the TGF-β1-mediated suppression of the inflammatory response has facilitated intensive research to evaluate the contribution of Smad7 in several immune-mediated pathologies.

Inhibitory Smads, including Smad6 and Smad7, are key regulators of TGF-beta/bone morphogenetic protein (BMP) signaling by negative feedback loops. They can form stable complexes with activated type I receptors and thereby blocking the phosphorylation of R-Smads, or recruit ubiquitin E3 ligases, such as Smurf1/2, resulting in the ubiquitination ...

In this study we report a novel mechanism whereby Smad7 antagonizes TGF-β signaling at the Smad level. Smad7 oligomerized with R-Smad proteins upon TGF-β signaling and directly inhibited R-Smad activity, as assessed by Gal4-luciferase reporter assays.

Jun 20, 2013 · In this study, we demonstrate that miR-21 lowers the expression of Smad 7 through translation inhibition rather than mRNA decay and that TGF-β activates the regulatory Smad 2 and 3 proteins by...

Aug 23, 2023 · In addition, we discuss the involvement of Smad7, an inhibitor of TGF-β1 signaling, in immune-mediated disorders (e.g., psoriasis, rheumatoid arthritis, MS, and inflammatory bowel diseases), as well as the discordant results of clinical trials with mongersen, an oral pharmaceutical compound containing a Smad7 antisense oligonucleotide, in ...

Then, 48 h after the second round of transfection, cells were assayed for migratory activity on an xCELLigence platform in the presence of TGF-β1. (C) Panc1 cells stably expressing HA-RAC1B (pR1B) or empty pCGN vector (V) (verified by immunoblotting in inset) were transfected twice with either 50 nM of Co siRNA or SMAD7 siRNA. Only TGFβ ...