title: sPLA2 IB induces human podocyte apoptosis via the M-type phospholipase A2 receptor.
abstract: The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with the PLA2R, sPLA2 IB induced podocyte apoptosis in a time- and concentration-dependent manner. sPLA2 IB-induced podocyte PLA2R upregulation was not only associated with increased ERK1/2 and cPLA2α phosphorylation but also displayed enhanced apoptosis. In contrast, PLA2R-silenced human podocytes displayed attenuated apoptosis. sPLA2 IB enhanced podocyte arachidonic acid (AA) content in a dose-dependent manner. These data indicate that sPLA2 IB has the potential to induce human podocyte apoptosis via binding to the PLA2R. The sPLA2 IB-PLA2R interaction stimulated podocyte apoptosis through activating ERK1/2 and cPLA2α and through increasing the podocyte AA content.
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Yangbin
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Division of Nephrology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wan
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, NY, USA.
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
authors.affiliation: Children's Renal Unit and Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, UK.
authors.forename: Moin A
authors.initials: MA
authors.lastname: Saleem
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D016718:Arachidonic Acid / Q000378:metabolism; D001706:Biopsy; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D054500:Group IB Phospholipases A2 / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D050199:Podocytes / Q000378:metabolism*; D011485:Protein Binding; D054507:Receptors, Phospholipase A2 / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; D016718:Arachidonic Acid; D054500:Group IB Phospholipases A2