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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