原发性膜性肾病中sPLA2-IB协同PLA2R-IgG作用于PLA2R促进足细胞损伤的机制研究

原发性膜性肾病(PMN)是一种发病机制尚不明确的自身免疫疾病。磷脂酶A2受体（PLA2R）是足细胞主要靶抗原，也是跨膜受体，具有信号转导功能，生信分析提示丙酮酸脱氢酶（PDH）可能是PLA2R介导PMN的重要下游靶分子。sPLA2-IB是PLA2R天然配体，同PLA2R-IgG与PMN关系密切，提示sPLA2-IB协同PLA2R-IgG诱导足细胞损伤。因此，我们假设，sPLA2-IB促进PLA2R-IgG作用于PLA2R上调PDH导致氧应激影响足细胞功能。本研究通过分析PMN患者及动物模型的血清和肾小球中sPLA2-ⅠB、PLA2R-IgG、PLA2R的关系，观察sPLA2-ⅠB对动物模型的影响，转染PLA2R突变质粒等方法，揭示sPLA2-ⅠB是否促进PLA2R-IgG结合PLA2R，及PLA2R-IgG是否通过PLA2R上调PDH导致氧应激促进足细胞损伤，具有重要临床意义

Primary membranous nephropathy (PMN) is an autoimmune disease with unclear pathogenesis. Phospholipase A2 receptor (PLA2R) is the main target antigen of podocytes as well as a transmembrane receptor with signal transduction functions. Bioinformatics analysis suggests that pyruvate dehydrogenase (PDH) may be an important downstream target molecule of PLA2R-mediated PMN. sPLA2-IB is a natural ligand of PLA2R and is closely related to PMN, like as PLA2R-IgG, suggesting that sPLA2-IB cooperates with PLA2R-IgG to induce podocyte damage. Therefore, we hypothesize that PLA2R-IgG affects podocyte function by acting on PLA2R through upregulating PDH abnormal oxidative phosphorylation and is enhanced by sPLA2-IB. In this study, the relationship between sPLA2-ⅠB, PLA2R-IgG and PLA2R in the serum and glomeruli of PMN patients and animal models was analyzed, and the effects of sPLA2-ⅠB on animal models were observed. Methods such as transfection of PLA2R mutant plasmids revealed that Whether sPLA2-ⅠB promotes PLA2R-IgG binding to PLA2R, and whether PLA2R-IgG promotes podocyte damage through PLA2R-mediated oxygen stress via PDH, which has important clinical significance.