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Loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation

Loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation

作     者:Xu-Feng Lu Yong-Jie Zhou Lei Zhang Hong-Jie Ji Li Li Yu-Jun Shi Hong Bu 

作者机构:Laboratory of PathologyWest China HospitalSichuan University Regenerative Medicine Research CenterWest China HospitalSichuan University Department of PathologyWest China HospitalSichuan University 

出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))

年 卷 期:2015年第21卷第21期

页      面:6591-6603页

核心收录:

学科分类:1002[医学-临床医学] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基  金:Supported by National Key Clinical Project,and National Sciences and Technology Major Project of China,No.2012ZX10002-017 

主  题:Dicer1 microRNAs Liver inflammation Liver fibrosis Hepatocellular carcinoma 

摘      要:AIM:To investigate the continuous hepatic histopathological processes which occur in response to the loss of ***:We generated a hepatocyte-selective Dicer1 knockout mouse and observed the gradual hepatic histopathological changes in the mutant *** and Western blotting were performed to detect Dicer1 *** performed hematoxylin and eosin staining,Periodic acid-Schiff staining,Oil Red O staining,and Masson s trichrome staining to detect histological changes in Dicer1-deficient ***67 immunohistochemistry,terminal deoxynucleotidyl transferase-mediated d UTP nickend labeling assay,and Western blotting were used to determine hepatocyte proliferation and *** biochemistry,cytokine assays,and flow cytometric analysis were performed to quantity liver necrosis and *** markers were determined by Western blotting and q ***19,CD133,and OV6 immunofluorescence were used to observe liver progenitor *** and q PCR were performed to reveal embryonic gene *** also performed histological staining and Western blotting to analyze hepatocellular carcinoma(HCC) ***:Dicer1 inactivation resulted in significant architecture disorganization and metabolism disruptionin the ***1 disruption impaired hepatocyte survival and resulted in profound cell apoptosis and continuous *** contrast to previous reports,the mutant liver exhibited chronic inflammation and progressive fibrosis,and could not be repopulated by Dicer1-positive *** addition,extensive activation of hepatic progenitor cells was *** HCC was observed as early as 4 mo after ***:Hepatic loss of Dicer1 results in complex chronic pathological processes,including hepatocyte death,inflammatory infiltration,chronic fibrosis,compensatory proliferation,progenitor activation,and spontaneous hepatocarcinogenesis.

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