Antagonizing TGF-β induced liver fibrosis by a retinoic acid derivative through regulation of ROS and calcium influx

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 to...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-01, Vol.365 (3), p.484-489
Main Authors: Yang, Kun-Lin, Chang, Wen-Teng, Chuang, Chia-Chang, Hung, Kuo-Chen, Li, Eric I.C.
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Calcium - analysis
Calcium - metabolism
Calcium influx
Collagen Type II - metabolism
Cyclohexanes - chemistry
Cyclohexanes - pharmacology
Hepatic stellate cells (HSC)
Hydrodynamics-based gene delivery
Liver Cirrhosis, Experimental - metabolism
Liver Cirrhosis, Experimental - pathology
Mice
Mice, Inbred BALB C
Pentanoic Acids - chemistry
Pentanoic Acids - pharmacology
Phellinus linteus
Reactive oxygen species (ROS)
Reactive Oxygen Species - metabolism
TGF-β
Transforming Growth Factor beta - antagonists & inhibitors
Transforming Growth Factor beta - genetics
Tretinoin - pharmacology
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.10.203