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	Increased carbon tetrachloride-induced liver injury and fibrosis in FGFR4-deficient mice
	Yu, C. D. ; Wang, F. ; Jin, C. L. ; Wu, X. C. ; Chan, W. K. ; McKeehan, W. L. ; Yu CD(俞春东)
	2002
关键词	FIBROBLAST GROWTH-FACTOR PLASMINOGEN DEFICIENCY LEADS ACTIVATED PROTEIN-KINASE INDUCED HEPATOTOXICITY ETHANOL-CONSUMPTION CYTOCHROME-P450 2E1 HEPARAN-SULFATE DEGRADATION EXPRESSION CYP2E1
英文摘要	Carbon tetrachloride (CCl4) intoxification in rodents is a commonly used model of both acute and chronic liver injury. Recently, we showed that mice in which FGFR4 was ablated from the germline exhibited elevated cholesterol metabolism and bile acid synthesis coincident with unrepressed levels of cytochrome P450 7A (CYP7A), the rate-limiting enzyme in cholesterol disposal. of the four fibroblast growth factor (FGF) receptor genes expressed in adult liver, FGFR4 is expressed specifically in mature hepatocytes. To determine whether FGFR4 plays a broader role in liver-specific metabolic functions, we examined the impact of both acute and chronic exposure to CCl4 in FGFR4-deficient mice. Following acute CCl4 exposure, the FGFR4-deficient mice exhibited accelerated liver injury, a significant increase in liver mass and delayed hepatolobular repair. Chronic CCl4 exposure resulted in severe fibrosis in livers of FGFR4-deficient mice compared to normal mice. Analysis at both mRNA and protein levels indicated an 8-hour delay in FGFR4-deficient mice in the down-regulation of cytochrome P450 2E1 (CYP2E1) protein, the major enzyme whose products underlie CCl4-induced injury. These results show that hepatocyte FGFR4 protects against acute and chronic insult to the liver and prevents accompanying fibrosis. The results show that FGFR4 acts by promotion of processes that restore hepatolobular architecture rather than cellularity while limiting damage due to prolonged CYP2E1 activity.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/64987]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Yu, C. D.,Wang, F.,Jin, C. L.,et al. Increased carbon tetrachloride-induced liver injury and fibrosis in FGFR4-deficient mice[J],2002.
APA	Yu, C. D..,Wang, F..,Jin, C. L..,Wu, X. C..,Chan, W. K..,...&俞春东.(2002).Increased carbon tetrachloride-induced liver injury and fibrosis in FGFR4-deficient mice..
MLA	Yu, C. D.,et al."Increased carbon tetrachloride-induced liver injury and fibrosis in FGFR4-deficient mice".(2002).

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