title: Bioinformatics analysis of proteomic profiles during the process of anti-Thy1 nephritis.
abstract: Anti-Thy1 nephritis is a well-established experimental mesangial proliferative nephritis model. Exploring the molecular mechanisms of pathophysiology in anti-Thy1 nephritis may elucidate the pathogeneses of mesangial proliferation. We examined the roles and acting mechanisms of differentially expressed proteins (DEPs) by bioinformatics analysis of glomeruli proteomic profiles during the course of anti-Thy1 nephritis. In total, 108 DEPs were found by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), and 40 DEPs were identified by matrix-assisted laser desorption ionization/time of flight and liquid chromatography-MS. DEPs were classified into five clusters (Clusters 1-5), according to their expression trends using Cluster 3.0 software, involved in regulating biological processes such as the stress response, cell proliferation, apoptosis, energy metabolism, transport, and the actin cytoskeleton. The expression patterns of ten DEPs, distributed across five clusters, including AKR1A1, AGAT, ATP6V1B2, HIBADH, MDH1, MPST, NIT2, PRDX6, PSMB7, and TPI1, were validated by Western blotting. Based on Western blotting and immunohistochemistry, we also found that the DEP FHL2, which was primarily expressed in the mesangial region, was down-regulated on days 3 and 5, and up-regulated on day 10. In vitro, we found that FHL2 overexpression induced mesangial cell proliferation by increasing the number of S-phase cells and decreasing G2/M-phase cells, whereas inhibiting FHL2 had the opposite effect. This study explored novel DEPs and their expression patterns during anti-Thy1 nephritis, and elucidated FHL2's effect on mesangial cell proliferation. These results will contribute to our understanding of the pathogenesis of mesangial proliferation.
authors.affiliation: Department of Nephrology, State Key Lab of Kidney Diseases, General Hospital of PLA, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiaoluan
authors.initials: X
authors.lastname: Liu
authors.forename: Suozhu
authors.initials: S
authors.lastname: Shi
authors.forename: Huabin
authors.initials: H
authors.lastname: Su
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Bai
authors.forename: Guangyan
authors.initials: G
authors.lastname: Cai
authors.forename: Fuquan
authors.initials: F
authors.lastname: Yang
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Xie
authors.forename: Yunping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shujia
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Xie
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016000:Cluster Analysis; D004195:Disease Models, Animal; D007518:Isoantibodies; D060850:LIM-Homeodomain Proteins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D050527:Mesangial Cells / Q000166:cytology* / Q000187:drug effects; D009124:Muscle Proteins / Q000378:metabolism* / Q000494:pharmacology; D009393:Nephritis / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: C491381:Fhl2 protein, rat; D007518:Isoantibodies; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D011506:Proteins; D014157:Transcription Factors; C035678:anti-Thy antibody