Journal of Diabetes · Published 2026-08-01 · DOI 10.1111/1753-0407.70254
DanDan Xu, Liang Xu, LinLin Li
ABSTRACT Background Diabetic nephropathy (DN) is a leading cause of end‐stage renal disease. ELAVL1, an RNA‐binding protein, is involved in the regulation of genes closely associated with DN pathogenesis, whereas suPAR acts as a circulating mediator that promotes podocyte damage and contributes to proteinuric kidney disorders. However, whether ELAVL1 regulates suPAR release in DN remains unexplored. Methods Clinical samples from patients with DN were collected and analyzed. In vitro, podocytes were treated with high glucose, and ELAVL1 or PLAUR (encoding uPAR) was knocked down or overexpressed using lentiviral transduction. In db/db mice, podocyte‐specific manipulation of Elavl1 or Plaur was performed via adeno‐associated virus‐mediated delivery. Renal function was assessed by measuring the urinary albumin‐to‐creatinine ratio (UACR) and serum creatinine. Glomerular pathology and inflammatory markers were evaluated histologically and biochemically. Results ELAVL1 was upregulated in DN and positively correlated with podocyte injury. Knockdown of ELAVL1 mitigated hyperglycemia‐induced podocyte damage and inflammatory responses. Mechanistically, ELAVL1 directly bound to and stabilized PLAUR mRNA, leading to increased uPAR protein expression and elevated suPAR secretion. The protective effects of ELAVL1 knockdown were reversed by PLAUR overexpression in podocytes. In diabetic mice, podocyte‐specific knockdown of Elavl1 or Plaur markedly lowered circulating suPAR levels and alleviated renal dysfunction and histopathological injury. Moreover, restoration of the PLAUR‐suPAR axis abolished the renoprotective benefits conferred by Elavl1 knockdown. Conclusion Hyperglycemia‐induced ELAVL1 upregulates PLAUR and suPAR release from podocytes, promoting renal inflammation and injury. Targeting the ELAVL1‐PLAUR‐suPAR axis may offer a therapeutic strategy for DN.
Abstract from DOAJ. Public domain (CC0 1.0).
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Xu, D., Xu, L., Li, L. (2026). The ELAVL1 ‐ PLAUR ‐ suPAR Axis Exacerbates Diabetic Nephropathy by Promoting Podocyte Injury and Inflammation. Journal of Diabetes. https://doi.org/10.1111/1753-0407.70254