Hepatocyte-Specific Deletion of Cdc42 Results in Delayed Liver Regeneration After Partial Hepatectomy in Mice

	Hepatocyte-Specific Deletion of Cdc42 Results in Delayed Liver Regeneration After Partial Hepatectomy in Mice
	Yuan, HX; Zhang, H; Wu, XW; Zhang, Z; Du, D; Zhou, WC; Zhou, SH; Brakebusch, C; Chen, ZJ
刊名	HEPATOLOGY
	2009
卷号	49 期号:1 页码:240-249
通讯作者	Chen, ZJ (reprint author), Shanghai Inst Biochem & Cell Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,zjchen@sibs.ac.cn
英文摘要	Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42 in regulating liver regeneration. Using a mouse model with liver-specific knockout of Cdc42 (Cdc42LK), we studied liver regeneration after partial hepatectomy. Histological analysis, immunostaining, and western blot analysis were performed to characterize Cdc42LK livers and to explore the role of Cdc42 in liver regeneration. In control mouse livers, Cdc42 became activated between 3 and 24 hours after partial hepatectomy. Loss of Cdc42 led to a significant delay of liver recovery after partial hepatectomy, which was associated with reduced and delayed DNA synthesis indicated by 5-bromo-2'-deoxyuridine staining. Consistent with this, expression of cyclins D1, A, and E was markedly delayed or reduced in Cdc42LK livers during regeneration. As a potential effector of Cdc42, Rac1 activation was dramatically attenuated in Cdc42LK livers after partial hepatectomy, suggesting it is regulated in a Cdc42-dependent manner. Activation of certain proliferative signaling pathways, such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p70S6 kinase pathways, was delayed in Cdc42LK livers. In addition, dilated bile canaliculi and excessive lipid accumulation were observed in mutant livers during liver regeneration, which may result from impaired cytoskeletal organization and intracellular trafficking in hepatocytes. Conclusion: Our results revealed important roles of Cdc42 in the regulation of proliferative signaling during liver regeneration. (HEPATOLOGY 2009;49:240-249.)
学科主题	Gastroenterology & Hepatology
类目[WOS]	Gastroenterology & Hepatology
关键词[WOS]	CYCLIN D1 EXPRESSION ; P70 S6 KINASE ; FARNESOID-X RECEPTOR ; DIRECTED MIGRATION ; RHO-GTPASES ; ACTIVATION ; RAC ; PROLIFERATION ; PATHWAY ; GROWTH
收录类别	SCI
语种	英语
WOS记录号	WOS:000262127400028
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1132]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yuan, HX,Zhang, H,Wu, XW,et al. Hepatocyte-Specific Deletion of Cdc42 Results in Delayed Liver Regeneration After Partial Hepatectomy in Mice[J]. HEPATOLOGY,2009,49(1):240-249.
APA	Yuan, HX.,Zhang, H.,Wu, XW.,Zhang, Z.,Du, D.,...&Chen, ZJ.(2009).Hepatocyte-Specific Deletion of Cdc42 Results in Delayed Liver Regeneration After Partial Hepatectomy in Mice.HEPATOLOGY,49(1),240-249.
MLA	Yuan, HX,et al."Hepatocyte-Specific Deletion of Cdc42 Results in Delayed Liver Regeneration After Partial Hepatectomy in Mice".HEPATOLOGY 49.1(2009):240-249.