Antagonizing TGF-beta induced liver fibrosis by a retinoic acid derivative through regulation of ROS and calcium influx.
Transforming growth factor-beta1 (TGF-beta1) 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, alpha-smooth muscle actin (alpha-SMA), and collagen 1A2, in an early liver fibrosis model we established previously where an inducible expression vector containing a TGF-beta 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.
Yang
Kun-Lin
KL
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Chang
Wen-Teng
WT
Chuang
Chia-Chang
CC
Hung
Kuo-Chen
KC
Li
Eric I C
EI
D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010421:Pentanoic Acids / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*
C525866:5-(2,2-dimethyl-6-methylenecyclohexyl)-3-methyl-2,4-pentadienoic acid; D000199:Actins; D024043:Collagen Type II; D003510:Cyclohexanes; D010421:Pentanoic Acids; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D002118:Calcium