Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-<i>β</i>1/Smad3 and TGF-<i>β</i>1/p38 MAPK Pathways.
Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-β1/Smad3 and autophagy pathway.
Furthermore, we detected the key factors involved in liver fibrosis in the mice, revealing significantly increased hydroxyproline concentration; elevated expression of α-smooth muscle actin (α-SMA) and fibrosis-related genes such as Collagen-1, Collagen-3, Mmp2, Mmp13, Timp1, Timp3, and Activin, upregulated Smad3 phosphorylation, and increased serum TGF-β levels.
Taken together, SAC attenuated CCl<sub>4</sub>-induced liver fibrosis in rats with anti-oxidant, anti-inflammatory and anti-fibrotic effects, and targeted STAT3/SMAD3 pathway to inhibit gene transcription.
With the severity of liver fibrosis, the expression of TGF-β, α-SMA, Smad3 and CTGF gradually increased, and the difference was statistically significant (p < 0.01).
Furthermore, MPOE ameliorated liver fibrosis as evidenced by the reduced expression of desmin, <i>α</i>-smooth muscle actin (<i>α</i>-SMA), transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1), and SMAD3 proteins.
The current study indicates that mirtazapine suppressed 5-HT-mediated TGF-β1/Smad3 and ERK1/2 signaling pathways as well as oxidative stress that contribute to the progression of liver fibrosis.
Here the authors show that ERG balances TGFβ signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a SMAD3-dependent mechanism.
Moreover, the NTSD treatment significantly decreased the transforming growth factor beta 1 (TGF-β1) and Smad3 gene expression and increased inhibitory Smad7 gene expression in liver tissues of HF rats, suggesting that NTSD inhibited the ECM expression of HSC by downregulating the TGF-β1/Smad signaling pathway.
In this review, we attempt to integrate recent advances in the understanding of the mechanisms underlying TGF-beta1/Smad3 pathway modulation of ECM gene expression in the context of liver fibrosis, discuss intervention strategies targeting the blockade of related signal pathways, and look into novel ways to the safe and efficacious prevention and treatment of hepatic fibrosis.