Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis

doi:10.1038/s41419-021-03443-y

	Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis
	Wu, Yuexin 1,2; Cao, Yuyan 1,2; Xu, Keren 2,3; Zhu, Yue 1,2; Qiao, Yuemei 1; Wu, Yanjun 1; Chen, Jianfeng 1,4; Li, Chen 3,5; Zeng, Rong3,6,7 ; Ge, Gaoxiang 1,4
	2021-02-08
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	12 期号:2 页码:#VALUE!
DOI	10.1038/s41419-021-03443-y
摘要	Liver cirrhosis remains major health problem. Despite the progress in diagnosis of asymptomatic early-stage cirrhosis, prognostic biomarkers are needed to identify cirrhotic patients at high risk developing advanced stage disease. Liver cirrhosis is the result of deregulated wound healing and is featured by aberrant extracellular matrix (ECM) remodeling. However, it is not comprehensively understood how ECM is dynamically remodeled in the progressive development of liver cirrhosis. It is yet unknown whether ECM signature is of predictive value in determining prognosis of early-stage liver cirrhosis. In this study, we systematically analyzed proteomics of decellularized hepatic matrix and identified four unique clusters of ECM proteins at tissue damage/inflammation, transitional ECM remodeling or fibrogenesis stage in carbon tetrachloride-induced liver fibrosis. In particular, basement membrane (BM) was heavily deposited at the fibrogenesis stage. BM component minor type IV collagen alpha 5 chain expression was increased in activated hepatic stellate cells. Knockout of minor type IV collagen alpha 5 chain ameliorated liver fibrosis by hampering hepatic stellate cell activation and promoting hepatocyte proliferation. ECM signatures were differentially enriched in the biopsies of good and poor prognosis early-stage liver cirrhosis patients. Clusters of ECM proteins responsible for homeostatic remodeling and tissue fibrogenesis, as well as basement membrane signature were significantly associated with disease progression and patient survival. In particular, a 14-gene signature consisting of basement membrane proteins is potent in predicting disease progression and patient survival. Thus, the ECM signatures are potential prognostic biomarkers to identify cirrhotic patients at high risk developing advanced stage disease.
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收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000617678300005
出版者	SPRINGERNATURE
WOS关键词	LIVER
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125815
专题	生命科学与技术学院_特聘教授组_曾嵘组
通讯作者	Li, Chen; Zeng, Rong; Ge, Gaoxiang
作者单位	1.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, CAS Key Lab Syst Biol, Shanghai 200031, Peoples R China; 4.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China; 5.Shanghai Jiao Tong Univ, Ctr Single Cell Omics, Sch Publ Hlth, Sch Med, Shanghai 200025, Peoples R China; 6.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, CAS Key Lab Syst Biol, Hangzhou 310024, Peoples R China; 7.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Wu, Yuexin,Cao, Yuyan,Xu, Keren,et al. Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis[J]. CELL DEATH & DISEASE,2021,12(2):#VALUE!.
APA	Wu, Yuexin.,Cao, Yuyan.,Xu, Keren.,Zhu, Yue.,Qiao, Yuemei.,...&Ge, Gaoxiang.(2021).Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis.CELL DEATH & DISEASE,12(2),#VALUE!.
MLA	Wu, Yuexin,et al."Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis".CELL DEATH & DISEASE 12.2(2021):#VALUE!.