Extracellular vesicle-derived TMEM106A participated in podocyte injury via EGR1 in preeclampsia.

Preeclampsia (PE), a pregnancy-specific hypertensive disorder affecting approximately 5-8% of pregnancies, is a leading cause of maternal and fetal morbidity and mortality. Although renal complications, particularly podocyte injury, are hallmarks of preeclampsia-related organ dysfunction, the underlying molecular mechanisms remain poorly understood. In this study, PE patients from the Gene Expression Omnibus (GEO) database (GSE192902) and injured podocytes from GSE124622 were used to select TMEM106A. Quantitative PCR (qPCR) revealed that TMEM106A expression was significantly downregulated in the urine of PE patients, and urinary TMEM106A levels were negatively correlated with nephrin, PCX, IL-1β, and TNF-α levels. Compared with the controls, podocytes exposed to extracellular vesicles (EVs) from PE patients exhibit reduced TMEM106A levels and aggravated podocyte injury. Silencing TMEM106A in vitro aggravated podocyte cytoskeleton rearrangement and inflammation, whereas its overexpression alleviated these responses. Transcriptomic analysis identified EGR1 as a downstream gene of TMEM106A. Mechanistically, TMEM106A silencing promoted podocyte injury via EGR1 upregulation. In vivo, podocyte-specific overexpression of TMEM106A alleviated renal injury in an L-NAME-induced PE mouse model, whereas podocyte-specific deletion of EGR1 conferred renal protection in the same model. These findings demonstrate that EV-derived TMEM106A modulates podocyte injury in PE by regulating EGR1 expression, highlighting a potential therapeutic axis for mitigating renal dysfunction in preeclampsia.