title: ERp57 is up-regulated in free fatty acids-induced steatotic L-02 cells and human nonalcoholic fatty livers.
abstract: Pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not clear. In this study we aimed to identify proteins involved in NAFLD development in free fatty acids (FFA)-induced hepatosteatotic cells and in human liver biopsies. Steatosis was induced by incubating a normal human hepatocyte-derived cell line L-02 with FFA. Differentially expressed proteins in the steatotic cells were analyzed by two-dimensional gel electrophoresis-based proteomics. Involvement of one of the up-regulated proteins in steatosis was characterized using the RNA interference approach with the steatotic cells. Protein expression levels in liver biopsies of patients with NAFLD were assessed by immunohistochemistry. Proteomic analysis of L-02 steatotic cells revealed the up-regulation of ERp57, a condition not previously implicated in NAFLD. Knockdown of ERp57 expression with siRNA significantly reduced fat accumulation in the steatotic cells. ERp57 expression was detected in 16 out of 17 patient biopsies and correlated with inflammation grades or fibrosis stages, while in 5 normal biopsies ERp57 expression was not detectable in hepatocytes. In conclusion, ERp57 was up-regulated in FFA-induced steatotic hepatic cells and in NAFLD patient livers and demonstrated steatotic properties in cultured cells. Further investigations are warranted to verify the involvement of ERp57 in NAFLD development.
authors.affiliation: Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Ping-Kei
authors.initials: PK
authors.lastname: Chan
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Pan
authors.forename: Kwok-Ho
authors.initials: KH
authors.lastname: Kwon
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Chu
authors.forename: Wang-Fun
authors.initials: WF
authors.lastname: Fong
authors.forename: Wilson M S
authors.initials: WM
authors.lastname: Tsui
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D015854:Up-Regulation
chemical_list: D005230:Fatty Acids, Nonesterified; D011506:Proteins; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human