Transforming growth factor-beta induces contraction of activated hepatic stellate cells

Journal of Hepatology
Kusum K KharbandaDean J Tuma

Abstract

Transforming growth factor-beta (TGF-beta) is a cytokine produced in abundance during liver injury. Recognizing the prominent roles that hepatic stellate cells (HSCs) and TGF-beta play in portal hypertension and fibrogenesis, respectively, we sought to evaluate the effect of TGF-beta on the contractility of activated HSCs. Spontaneous immortalized cell lines of HSC origin were used in this study. Cells were grown in three-dimensional collagen gel lattice, transferred to 60 mm dishes and exposed to varying concentrations of TGF-beta1 in serum-free medium at 37 degrees C for up to 120 h. The area of the floating gels was measured using a Fluor S-MultiImager (Biorad), the cellular smooth muscle-alpha actin (SMA) content quantified and PKC activation studies conducted. TGF-beta1 induced a time- and dose-dependent decrease in lattice area up to 40% of control (P<0.05) that reflects the contraction of activated HSCs. This induced contraction was associated with increases in SMA content (3-fold, P<0.05) and PKC activation (5-fold, P<0.05) in these cells. Furthermore, pre-incubating with a PKC--specific inhibitor completely abrogated the TGF-beta-induced contraction. TGF-beta induces contraction of activated HSCs via an increase in SMA...Continue Reading

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Citations

Jan 21, 2014·Environmental Toxicology and Pharmacology·Xiaokun PeiZhifeng Liu
Nov 3, 2010·Journal of Gastroenterology and Hepatology·Hui-Ying RaoXu Cong
Sep 12, 2007·Liver International : Official Journal of the International Association for the Study of the Liver·Yoshimasa KobayashiBruce R Bacon
Jan 7, 2014·Mayo Clinic Proceedings·Mariana Verdelho Machado, Anna Mae Diehl
Feb 8, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Ratchadaporn NamsenSaranyapin Potikanond
Dec 14, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Franck ChiappiniAntoinette Lemoine
Jan 28, 2015·World Journal of Gastroenterology : WJG·Perla Oliveira SchulzLuiz Arnaldo Szutan
Jun 3, 2021·International Journal of Molecular Sciences·Andrés TabernillaMathieu Vinken
Nov 6, 2008·Clinics in Liver Disease·Russell K Soon, Hal F Yee

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