Smad2 increases the apoptosis of activated human hepatic stellate cells induced by TRAIL

International Immunopharmacology
Fengyun XuLei Zhang

Abstract

The activation of hepatic stellate cells (HSCs) plays a critical role in the development of liver fibrosis. The induction of apoptosis in activated HSCs during the recovery phase of hepatic fibrosis represents a potential anti-fibrotic therapy. We have previously shown that Smad2 protects against hepatic fibrogenesis; however, the role of Smad2 in the regulation of activated HSC apoptosis remains unknown. We hypothesized that Smad2 regulates the apoptosis of activated HSCs, leading to the resolution of liver fibrosis. To test this hypothesis, the livers of rats were harvested at 0 and 4 weeks after hepatic fibrosis was established by CCl4 injection. Furthermore, TGF-β1-activated HSCs were treated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) following the silencing or overexpression of Smad2. Both the phosphorylation of Smad2 and TRAIL were detected in fibrotic liver tissues. The results of TUNEL and α-SMA double-staining showed an increase in the apoptosis of activated HSCs during the spontaneous recovery phase. The knockdown of Smad2 reduced TRAIL-induced apoptosis in TGF-β1-activated human LX-2 cells and resulted in an increased expression of α-SMA and collagen I (Col. I). In contrast, the overexpressi...Continue Reading

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Citations

Nov 14, 2019·Cells·Bedair DewidarAnd Nadja Meindl-Beinker
Oct 27, 2018·International Journal of Oncology·Norahayu Othman, Noor Hasima Nagoor
Jul 19, 2017·Scientific Reports·Harsimran D SinghMala K Maini
Apr 9, 2020·Cells·Natascha RoehlenThomas F Baumert
Apr 20, 2018·Mediators of Inflammation·David M HabielCory M Hogaboam
Aug 31, 2019·Biochemistry and Biophysics Reports·Munkhzul GanboldHiroko Isoda

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