气候变化领域集成服务门户(CCPortal): Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis

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DOI	10.1073/pnas.2019633118
	Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis
	Nishimura N.; De Battista D.; McGivern D.R.; Engle R.E.; Tice A.; Fares-Gusmao R.; Kabat J.; Pomerenke A.; Nguyen H.; Sato S.; Bock K.W.; Moore I.N.; Kleiner D.E.; Zamboni F.; Alter H.J.; Govindarajan S.; Farci P.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Older age at the time of infection with hepatitis viruses is associated with an increased risk of liver fibrosis progression. We hypothesized that the pace of fibrosis progression may reflect changes in gene expression within the aging liver. We compared gene expression in liver specimens from 54 adult donors without evidence of fibrosis, including 36 over 40 y old and 18 between 18 and 40 y old. Chitinase 3-like 1 (CHI3L1), which encodes chitinase-like protein YKL-40/CHI3L1, was identified as the gene with the greatest age-dependent increase in expression in liver tissue. We investigated the cellular source of CHI3L1 in the liver and its function using liver tissue specimens and in vitro models. CHI3L1 expression was significantly higher in livers of patients with cirrhosis of diverse etiologies compared with controls represented by patients who underwent liver resection for hemangioma. The highest intrahepatic CHI3L1 expression was observed in cirrhosis due to hepatitis D virus, followed by hepatitis C virus, hepatitis B virus, and alcohol-induced cirrhosis. In situ hybridization of CHI3L1 messenger RNA (mRNA) identified hepatocytes as the major producers of CHI3L1 in normal liver and in cirrhotic tissue, wherein hepatocytes adjacent to fibrous septa showed higher CHI3L1 expression than did those in more distal areas. In vitro studies showed that recombinant CHI3L1 promotes proliferation and activation of primary human hepatic stellate cells (HSCs), the major drivers of liver fibrosis. These findings collectively demonstrate that CHI3L1 promotes liver fibrogenesis through a direct effect on HSCs and support a role for CHI3L1 in the increased susceptibility of aging livers to fibrosis progression. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Aging; CHI3L1; Cirrhosis; Liver fibrosis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179716
作者单位	Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, United States; Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, United States; Biological Imaging Facility Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, United States; Infectious Disease Pathogenesis Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, United States; Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, United States; Liver Transplantation Center, Azienda Ospedaliera Brotzu, Cagliari, 09134, Italy; Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, MD 20892, United States; Department of Pathology, Rancho Los Amigos Hospital, University of Southern California, Los Angeles, CA 90242, United States
推荐引用方式 GB/T 7714	Nishimura N.,De Battista D.,McGivern D.R.,et al. Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis[J],2021,118(17).
APA	Nishimura N..,De Battista D..,McGivern D.R..,Engle R.E..,Tice A..,...&Farci P..(2021).Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Nishimura N.,et al."Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).