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学科主题: 基础医学
题名:
Comparative proteomic study reveals 17 beta-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease
作者: Su, Wen1; Wang, Yang2,3; Jia, Xiao1; Wu, Wenhan4; Li, Linghai2; Tian, Xiaodong4; Li, Sha1; Wang, Chunjiong1; Xu, Huamin1; Cao, Jiaqi1; Han, Qifei1; Xu, Shimeng2,3; Chen, Yong2; Zhong, Yanfeng5,6; Zhang, Xiaoyan7; Liu, Pingsheng2; Gustafsson, Jan-Ake8; Guan, Youfei1,7
关键词: lipogenesis ; SCDR9 ; HSDI7 beta 13
刊名: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
发表日期: 2014-08-05
DOI: 10.1073/pnas.1410741111
卷: 111, 期:31, 页:11437-11442
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: ASIA-PACIFIC REGION ; MAMMARY EPITHELIAL-CELLS ; LIPID DROPLETS ; ENDOPLASMIC-RETICULUM ; 17-BETA-HYDROXYSTEROID-DEHYDROGENASE ; MEMBRANE ; INHIBITORS ; DEHYDROGENASES ; MITOCHONDRIA ; ORGANELLE
英文摘要:

Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive accumulation of lipid droplets (LDs). The aim of this study was to determine the function of 17 beta-hydroxysteroid dehydrogenase-13 (17 beta-HSD13), one of our newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development LDs were isolated from 21 human liver biopsies, including 9 cases with normal liver histology (group 1) and 12 cases with simple steatosis (group 2). A complete set of LD-associated proteins from three liver samples of group 1 or group 2 were determined by 2D LC-MS/MS. By comparing the LD-associated protein profiles between subjects with or without NAFLD, 54 up-regulated and 35 down-regulated LD-associated proteins were found in NAFLD patients. Among them, 17 beta-HSD13 represents a previously unidentified LD-associated protein with a significant up-regulation in NAFLD. Because the 17 beta-HSD family plays an important role in lipid metabolism, 17 beta-HSD13 was selected for validating the proteomic findings and exploring its role in the pathogenesis of NAFLD. Increased hepatic 17 beta-HSD13 and its LD surface location were confirmed in db/db (diabetic) and high-fat diet-fed mice. Adenovirus-mediated hepatic overexpression of human 17 beta-HSD13 induced a fatty liver phenotype in C57BL/6 mice, with a significant increase in mature sterol regulatory element-binding protein 1 and fatty acid synthase levels. The present study reports an extensive set of human liver LD proteins and an array of proteins differentially expressed in human NAFLD. We also identified 17 beta-HSD13 as a pathogenic protein in the development of NAFLD.

语种: 英语
所属项目编号: 2012CB517504 ; 2011CBA009000 ; 2010CB912500 ; 2011ZX09102-011-12 ; 81030003 ; 81390351 ; 81121061 ; 81270932 ; 61273228 ; 81270275 ; 81200511 ; E-0004
项目资助者: Ministry of Science and Technology ; Natural Science Foundation ; Robert A. Welch Foundation
WOS记录号: WOS:000339807200047
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67641
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
2.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Peking Univ, Hosp 1, Dept Surg, Beijing 100044, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China
6.Peking Univ, Beijing Autopsy Ctr, Beijing 100191, Peoples R China
7.Shenzhen Univ, Hlth Sci Ctr, Dept Physiol, Shenzhen 518060, Peoples R China
8.Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX 77204 USA

Recommended Citation:
Su, Wen,Wang, Yang,Jia, Xiao,et al. Comparative proteomic study reveals 17 beta-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2014,111(31):11437-11442.
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