Antagonizing TGF-beta induced liver fibrosis by a retinoic acid derivative through regulation of ROS and calcium influx |
| |
Authors: | Yang Kun-Lin Chang Wen-Teng Chuang Chia-Chang Hung Kuo-Chen Li Eric I C |
| |
Institution: | a Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan b Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan 717, Taiwan c Department of Emergency Medicine, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan d Department of General Surgery, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan e Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan |
| |
Abstract: | Transforming growth factor-beta1 (TGF-β1) mediates the regulation of extracellular matrix via reactive oxygen species (ROS) and calcium influx, both are activators of hepatic stellate cells (HSC) which play a critical role in hepatic fibrogenesis. Hence one can use ROS assay as the main screening tool for molecules that might antagonize the process of liver fibrosis. A retinoic acid derivative isolated from the mycelium of Phellinus linteus that down-regulates ROS generation and calcium influx in HSC-T6 cells was thus obtained in our screening process. The retinoic acid derivative also reverses an early liver fibrosis, as assayed by liver contents of hydroxyproline, α-smooth muscle actin (α-SMA), and collagen 1A2, in an early liver fibrosis model we established previously where an inducible expression vector containing a TGF-β gene was hydrodynamically transferred into a testing animal. Retinoic acid derivative thus acts both in vitro and in vivo to prevent liver fibrosis at an early phase. |
| |
Keywords: | Reactive oxygen species (ROS) Hepatic stellate cells (HSC) TGF-β Hydrodynamics-based gene delivery Calcium influx |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|