title: FHL2-driven molecular network mediated Septin2 knockdown inducing apoptosis in mesangial cell.
abstract: The apoptosis of mesangial cells (MCs) plays a critical role in the pathological progress of MesPGN. Septin2, a filamentous GTPase, is implicated in the apoptotic progress of MCs in the rat MesPGN model. However, the molecular mechanism of SEPT2 in MCs apoptosis is not clear. Here, we present the FHL2-driven molecular network as the main mechanism of SEPT2-mediated rat primary MCs apoptosis. First, we proved that the expression of FHL2 and Septin2 were closely related with MCs apoptosis in anti-Thy1 nephritis model. Then, it was found that FHL2 was a new interaction protein of Septin2 and Septin2 knockdown could induce MC apoptosis by FHL2-mediatied signal pathways including p-ERK1 and p-AKT. We applied label-Free quantitative proteomics to identify the mechanism of Septin2/FHL2-regulated apoptosis. Bioinformatics analysis revealed that FHL2-driven molecular network composed of biological functions including glycolysis, oxidative stress, ribonucleotide metabolism, actin cytoskeleton regulation, and signaling pathway, was the main mechanism of SETP2-mediated apoptosis. Furthermore, we showed that the effect of Septin2 knockdown on MC apoptosis could be alleviated by the overexpression of FHL2. Overall, this study illustrated the FHL2-driven molecular network controlling SEPT2-mediated apoptosis in MCs and their potential roles in mesangial proliferative nephritis.
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Guangyan
authors.initials: G
authors.lastname: Cai
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Cui
authors.forename: Wenjia
authors.initials: W
authors.lastname: Geng
authors.forename: Dapeng
authors.initials: D
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Wen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fujian
authors.initials: F
authors.lastname: Zhang
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Xie
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D050527:Mesangial Cells / Q000166:cytology* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D051381:Rats; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C491381:Fhl2 protein, rat; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D009414:Nerve Growth Factors; D014157:Transcription Factors; C571123:septin2 protein, rat; D058112:Septins
keywords: Apoptosis; Cell biology; FHL2; Mesangial cell; Proteomics; Septin2