Deletion of clock gene Per2 exacerbates cholestatic liver injury and fibrosis in mice

被引：34

作者：

Chen, Peng ^{[1
]}

Kakan, Xiamusiya ^{[2
]}

Wang, Shiming ^{[1
]}

Dong, Wei ^{[1
]}

Jia, Aiqun ^{[1
]}

Cai, Chun ^{[1
]}

Zhang, Jianfa ^{[1
]}

机构：

[1] Nanjing Univ Sci & Technol, Ctr Mol Metab, Nanjing 210094, Jiangsu, Peoples R China

[2] Xinjiang Agr Univ, Dept Agr, Urumqi 830052, Peoples R China

来源：

EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY | 2013年 / 65卷 / 04期

基金：

美国国家科学基金会;

关键词：

Per2; Cholestasis; Bile duct ligation; MECHANISMS; WEB;

D O I：

10.1016/j.etp.2011.12.007

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

The Period 2 (Per2) gene is an important component of the circadian system and is thought to modulate many physiological and pathological processes in mammals. In the previous study, we have disclosed the protective role of Per2 against carbon tetrachloride induced liver injury and fibrosis. Here we further assess the effect of Per2 deficiency on cholestatic hepatic injury and fibrosis. Cholestasis was induced by bile duct ligation (BDL) for 10 days in wild-type (WT) and Per2(-/-) mice. Masson trichrome staining and analysis of alpha-SMA immunohistochemistry were performed to show the collagen accumulation and the HSC activation, respectively. The mRNA levels of fibrosis-related genes were monitored by quantitative real-time PCR. Following BDL, livers from Per2(-/-) mice exhibited markedly increased extent of bile infarct and extracellular matrix (ECM) deposition compared with WT mice. Furthermore, the expressions of fibrosis-related genes like TNF-alpha, TGF-beta 1, Col1 alpha 1 and TIMP-1 were dramatically elevated in Per2(-/-) cholestatic liver. Our observations indicated that clock gene Per2 plays a protective role in mediating liver injury and fibrosis during cholestasis. (C) 2011 Elsevier GmbH. All rights reserved.

引用

页码：427 / 432

页数：6

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