Introduction Podocyte loss or functional impairment is a key event in the pathophysiology of nephrotic syndrome (NS). NS can further progress to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). This study aimed to explore the potential role and underlying mechanism of TRIM37 in NS. Methods Bioinformatics analysis was performed on the GEO dataset GSE97709 to analyze the association between TRIM37 expression and CKD. Adriamycin (ADR)-induced nephropathy models in mice and ADR-exposed human podocytes were used to investigate the function of TRIM37. TRIM37 overexpression experiments were conducted in vivo and in vitro . The binding interaction between TRIM37 and PTEN was verified and the ubiquitination and degradation of PTEN. The activation of the Akt pathway were detected. PTEN overexpression was used to confirm the regulatory relationship with TRIM37. Results Both ADR-treated mice and ADR-exposed podocytes showed decreased TRIM37 expression. In vivo , ADR-induced mice exhibited elevated proteinuria, renal dysfunction, and structural damage, which were significantly ameliorated by TRIM37 overexpression. TRIM37 also inhibited ADR-induced cell apoptosis. In vitro , ADR exposure caused podocyte injury, reduced cell viability, and altered mitochondrial membrane potential, while these effects were partially reversed by TRIM37 overexpression. Mechanistically, TRIM37 directly bound to PTEN, promoting its ubiquitination and subsequent degradation, thereby activating the Akt pathway. Furthermore, PTEN overexpression counteracted the protective effects of TRIM37. Discussion The findings demonstrate that TRIM37 attenuates ADR-induced nephropathy by inhibiting mitochondrial apoptosis and podocyte injury through the PTEN/Akt signaling pathway. Collectively, these results suggest that TRIM37 may serve as a potential therapeutic target for NS.
Xin et al. (2026) studied this question.