The effect of Smad2- and Smad3-targeting RNA interference on extracellular matrix synthesis in rat fibroblasts of peritoneal adhesion tissues.

The effect of Smad2- and Smad3-targeting RNA interference on extracellular matrix synthesis in rat fibroblasts of peritoneal adhesion tissues.
Am J Transl Res. 2020;12(11):7420-7429
Authors: Zeng X, Lu B, Wang F, Mao J, Deng L, Li Y, Hou L
Abstract
Fibroblasts migrating to peritoneum injuries play an important role in the development of postoperative peritoneal adhesions due to the excessive synthesis and deposition of extracellular matrix (ECM). This effect is mainly induced by the transforming growth factor-β (TGF-β). Studies indicate that elevated TGF-β1 levels and TGF-β1/Smad signaling are both implicated in the formation of peritoneal adhesions. To confirm the effect of TGF-β1/Smad signaling interference in regulating excessive ECM synthesis, a total of four different R-Smad-targeting small interference RNA (siRNA) duplexes (Smad2-500, Smad2-956, Smad3-378, Smad3-1385) were tested in this study using a TGF-β1-stimulated adhesion tissue fibroblasts (ATFs) cell model. The in vitro assessments show that all proposed siRNAs are capable of significantly downregulating the mRNA and protein levels of Smad2 and Smad3 in ATFs. They also inhibit the phosphorylation of both Smads, which confirms their effect in blocking the TGF-β1/Smad signaling pathway. Moreover, the siRNA duplexes can appreciably lower the elevated levels of fibronectin and collagen 3 alpha 1 (COL3A1) in TGF-β1-stimulated ATFs, and the Smad3-378 siRNA can actuall...

Source: American Journal of Translational Research - December 15, 2020 Category: Research Tags: Am J Transl Res Source Type: research