Pericentral Hepatocytes Produce Insulin-Like Growth Factor-2 to Promote Liver Regeneration During Selected Injuries in Mice

doi:10.1002/hep.29340

	Pericentral Hepatocytes Produce Insulin-Like Growth Factor-2 to Promote Liver Regeneration During Selected Injuries in Mice
	Liu, Junlai1,2,3 ; Hu, Xiao 2; Chen, Jie 4; Li, Xinqi1,2,3 ; Wang, Lu1 ; Wang, Binbin1,2,3 ; Peng, Wenbo1,2,3 ; Yang, Cuiwei1,2,3 ; Li, Zhijie1,2,3 ; Chen, Yan 5; Wang, Yue J.6; Li, Chuanjiang 5; Li, Xiajun1 ; Yan, Fang 7; Wang, Yunfang 7; Shang, Changzhen 4; Wang, Xin 8,9,10; Chen, Tao 4; Huang, Pengyu1
	2017-12
发表期刊	HEPATOLOGY (IF:12.9[JCR-2023],15.5[5-Year])
ISSN	0270-9139
卷号	66 期号:6 页码:2002-2015
发表状态	已发表
DOI	10.1002/hep.29340
摘要	Liver regeneration (LR) happens after various types of injuries. Unlike the well-studied LR caused by partial hepatectomy (PHx), there is accumulating evidence suggesting that LR during other injuries may result from unknown mechanisms. In this study, we found that insulin-like growth factor 2 (IGF-2) was drastically induced following the liver injuries caused by tyrosinemia or longterm treatments of CCl4. However, this was not observed during the early phase of acute liver injuries after PHx or single treatment of CCl4. Remarkably, most IGF-2-expressing hepatocytes were located at the histological area around the central vein of the liver lobule after the liver injuries caused either in fumarylacetoacetate hydrolase-deficient mice or in CCl4 chronically treated mice. Hepatocyte proliferation in vivo was significantly promoted by induced IGF-2 overexpression, which could be inhibited by adeno-associated virus-delivered IGF-2 short hairpin RNAs or linsitinib, an inhibitor of IGF-2 signaling. Proliferating hepatocytes in vivo responded to IGF-2 through both insulin receptor and IGF-1 receptor. IGF-2 also significantly promoted DNA synthesis of primary hepatocytes in vitro. More interestingly, the significantly induced IGF-2 was also found to colocalize with glutamine synthetase in the region enriched with proliferating hepatocytes for the liver samples from patients with liver fibrosis. Conclusion: IGF-2 is produced by pericentral hepatocytes to promote hepatocyte proliferation and repair tissue damage in the setting of chronic liver injury, which is distinct from the signaling that occurs post-PHx.
收录类别	SCI
语种	英语
资助项目	Science and Technology Program of Guangzhou, China (STPG)[2016201604030054]
WOS研究方向	Gastroenterology & Hepatology
WOS类目	Gastroenterology & Hepatology
WOS记录号	WOS:000415922700056
出版者	WILEY
WOS关键词	HEPATIC PROGENITOR CELLS ; HUMAN HEPATOCELLULAR CARCINOMAS ; EMBRYONIC STEM-CELLS ; ADULT-RAT LIVER ; SELF-RENEWAL ; CHROMOSOMAL INSTABILITY ; SIGNAL TRANSDUCER ; KERATIN 19 ; CANCER ; INFLAMMATION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/14283
专题	生命科学与技术学院生命科学与技术学院_PI研究组_李夏军组生命科学与技术学院_PI研究组_黄鹏羽组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Chen, Tao; Huang, Pengyu
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Huaxia Middle Rd, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Hepatobiliary Surg, 33 Ying Feng Rd, Guangzhou 510289, Guangdong, Peoples R China 5.Southern Med Univ, Nanfang Hosp, Dept Hepatobiliary Surg, Guangzhou, Guangdong, Peoples R China 6.Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA 7.Beijing Inst Transfus Med, Stem Cell & Tissue Engn Lab, Beijing, Peoples R China 8.Inner Mongolia Univ, Natl Educ Minist Mammalian Reprod Biol & Biotechn, Key Lab, Hohhot, Peoples R China 9.Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA 10.Hepatoscience Inc, Sunnyvale, CA USA
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Liu, Junlai,Hu, Xiao,Chen, Jie,et al. Pericentral Hepatocytes Produce Insulin-Like Growth Factor-2 to Promote Liver Regeneration During Selected Injuries in Mice[J]. HEPATOLOGY,2017,66(6):2002-2015.
APA	Liu, Junlai.,Hu, Xiao.,Chen, Jie.,Li, Xinqi.,Wang, Lu.,...&Huang, Pengyu.(2017).Pericentral Hepatocytes Produce Insulin-Like Growth Factor-2 to Promote Liver Regeneration During Selected Injuries in Mice.HEPATOLOGY,66(6),2002-2015.
MLA	Liu, Junlai,et al."Pericentral Hepatocytes Produce Insulin-Like Growth Factor-2 to Promote Liver Regeneration During Selected Injuries in Mice".HEPATOLOGY 66.6(2017):2002-2015.