{"title":"PLA2R1 Overexpression Causes Podocyte Injury by Inhibiting the Cell Cycle: A Clinical Cross-Sectional Investigation and Cellular Study.","authors":"Wei Liang, Hua Zhang, Yi Wu, Zhiwei Lai, Weiqiang Zhang, Yuhao Cao, Lishan Tan, Zibo Xiong, Guang Yang, Zuying Xiong","doi":"10.2147/IJNRD.S523129","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>Phospholipase A2 receptor 1 (PLA2R1) is often overexpressed in 70% of primary membranous nephropathy (PMN) patients, with serum PLA2R1 antibodies and podocyte PLA2R1 antigens serving as key diagnostic markers. However, a minority of patients test positive for only the PLA2R1 antigen and negative for PLA2R1 antibodies, presenting distinct characteristics. This study investigated the underlying features and mechanisms in PLA2R1 antigen-positive PMN patients.</p><p><strong>Methods: </strong>26 patients' information was screened for analysis. And the effects of PLA2R1 overexpression on human podocytes (HPCs) was studied through cell experiments.</p><p><strong>Results: </strong>Clinical observations revealed that the median age of the 26 patients was 48.5 years, and the median onset time was 135 days. There was a significant negative correlation between blood albumin and antigen intensity. Cell studies demonstrated that PLA2R1 overexpression inhibited the proliferation and viability of HPCs. RNA sequencing and FACS assays revealed that PLA2R1 overexpression arrests HPCs at the S and G2/M phases.</p><p><strong>Conclusion: </strong>PLA2R1 overexpression affects the course of the PMN by inhibiting the podocyte cycle. This study suggests that PLA2R1-related PMN pathogenesis could involve an additional immune response, offering insights into PMN treatment development.</p>","PeriodicalId":14181,"journal":{"name":"International Journal of Nephrology and Renovascular Disease","volume":"18 ","pages":"163-175"},"PeriodicalIF":2.1000,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165200/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Nephrology and Renovascular Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/IJNRD.S523129","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: Phospholipase A2 receptor 1 (PLA2R1) is often overexpressed in 70% of primary membranous nephropathy (PMN) patients, with serum PLA2R1 antibodies and podocyte PLA2R1 antigens serving as key diagnostic markers. However, a minority of patients test positive for only the PLA2R1 antigen and negative for PLA2R1 antibodies, presenting distinct characteristics. This study investigated the underlying features and mechanisms in PLA2R1 antigen-positive PMN patients.
Methods: 26 patients' information was screened for analysis. And the effects of PLA2R1 overexpression on human podocytes (HPCs) was studied through cell experiments.
Results: Clinical observations revealed that the median age of the 26 patients was 48.5 years, and the median onset time was 135 days. There was a significant negative correlation between blood albumin and antigen intensity. Cell studies demonstrated that PLA2R1 overexpression inhibited the proliferation and viability of HPCs. RNA sequencing and FACS assays revealed that PLA2R1 overexpression arrests HPCs at the S and G2/M phases.
Conclusion: PLA2R1 overexpression affects the course of the PMN by inhibiting the podocyte cycle. This study suggests that PLA2R1-related PMN pathogenesis could involve an additional immune response, offering insights into PMN treatment development.
期刊介绍:
International Journal of Nephrology and Renovascular Disease is an international, peer-reviewed, open-access journal focusing on the pathophysiology of the kidney and vascular supply. Epidemiology, screening, diagnosis, and treatment interventions are covered as well as basic science, biochemical and immunological studies. In particular, emphasis will be given to: -Chronic kidney disease- Complications of renovascular disease- Imaging techniques- Renal hypertension- Renal cancer- Treatment including pharmacological and transplantation- Dialysis and treatment of complications of dialysis and renal disease- Quality of Life- Patient satisfaction and preference- Health economic evaluations. The journal welcomes submitted papers covering original research, basic science, clinical studies, reviews & evaluations, guidelines, expert opinion and commentary, case reports and extended reports. The main focus of the journal will be to publish research and clinical results in humans but preclinical, animal and in vitro studies will be published where they shed light on disease processes and potential new therapies and interventions.