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学科主题基础医学
Comparative proteomic study reveals 17 beta-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease
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
2014-08-05
DOI10.1073/pnas.1410741111
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
WOS记录号WOS:000339807200047
项目编号2012CB517504 ; 2011CBA009000 ; 2010CB912500 ; 2011ZX09102-011-12 ; 81030003 ; 81390351 ; 81121061 ; 81270932 ; 61273228 ; 81270275 ; 81200511 ; E-0004
资助机构Ministry of Science and Technology ; Natural Science Foundation ; Robert A. Welch Foundation
引用统计
被引频次:30[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67641
专题北京大学基础医学院_心血管所
北京大学基础医学院
北京大学第一临床医学院_普通外科
北京大学第一临床医学院_医学影像科
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
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GB/T 7714
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.
APA Su, Wen.,Wang, Yang.,Jia, Xiao.,Wu, Wenhan.,Li, Linghai.,...&Guan, Youfei.(2014).Comparative proteomic study reveals 17 beta-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,111(31),11437-11442.
MLA Su, Wen,et al."Comparative proteomic study reveals 17 beta-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.31(2014):11437-11442.
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