Study on the mechanism of apoptotic signal transduction of hepatocytes induced by TGF-?1 in liver cirrhosis mice
- VernacularTitle:TGF-?1诱导肝硬化小鼠肝细胞凋亡信号转导机制的研究
- Author:
Chunlei WANG
;
Zhiqiang HUANG
;
Ningxin ZHOU
;
Behrns KEVIN
- Publication Type:Journal Article
- Keywords:
APOPTOSIS;
LIVER CIRRHOSIS,EXPERIMENTAL;
TGF-?1
- From:
Chinese Journal of General Surgery
2001;0(08):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the relationships between apoptosis induced by transforming growth factor-beta 1(TGF-?1 )and caspase-3 as well as caspase-8 in liver cirrhosis mice. Methods In BALB/C mice,liver cirrhosis was induced by means of injection with 50% carbon tetrachloride for 8 weeks. Hepatocytes were isolated from normal and cirrhotic mice by means of a modified in situ collagenase solution perfusion method. The effects of caspase-3 and caspases-8 on TGF-?1-induced apoptosis were detected and compared . Results The viability of hepatocytes(isolated) from the mice by in situ two step collagenase digestion method was 95.2%. Internucleosomal(fragmented) DNA ladder was observed in TGF-?1 treated normal hepatocytes,but no obvious DNA ladder in(cirrhotic) hepatocytes was observed. The apoptotic rate in TGF-?1 treated normal hepatocytes (58.76%) was much higher than that of hepatocytes not treated with TGF-?1 (18.03%) .The apoptosis could be blocked by(Z-IETD-FMK) and(DEVD-CHO). Conclusions This study reveals that cirrhotic hepatocytes have poor response to(apoptosis) induced by TGF-?1,which indicates that inhibitory regulation of cell growth is impaired in cirrhotic hepatocytes. TGF-?1 can(induce) apoptosis of mice hepatocytes via caspase-8 and caspase-3-transducted signal(pathway).