CORO1A, A Novel Upregulated Protein in Renal Tubular Epithelial Cells of Diabetic Nephropathy, Participates in Regulating Vesicular Trafficking and the Ferroptosis Pathway

作者：Meng S, Xu X, Chen H, Zhang Z, Wu H, Qi C · 发表于：Nephrology (Carlton, Vic.) · 年份：2026 · DOI：10.1111/nep.70246 · 被引用次数：30 · 研究领域：Ferroptosis、Diabetic Nephropathies、Kidney Tubules、Epithelial Cells、Animals、Humans、Up-Regulation、Mice、Male、Cell Line、Signal Transduction

AIM: Diabetic nephropathy (DN) is characterised by progressive renal tubular epithelial cell injury, yet underlying molecular mechanisms remain incompletely understood. METHODS: Differentially expressed genes (DEGs) in DN were identified through integrated GEO dataset analysis (GSE30529 and GSE175759). Protein-protein interaction networks identified hub genes. GO and KEGG enrichment analyses determined molecular mechanisms. Nephroseq v5 explored correlations between hub genes and clinical features. CORO1A expression was validated by immunohistochemistry and western blot in DN patients, diabetic db/db mice and high glucose-exposed HK-2 cells. Vps34 inhibition and CORO1A knockdown explored regulatory mechanisms in vesicular trafficking and ferroptosis. RESULTS: Bioinformatics identified CORO1A as a phagosome-related core gene significantly upregulated in DN renal tubulointerstitium and correlated with eGFR, proteinuria, serum creatinine, blood pressure and age. External validation and experiments confirmed CORO1A upregulation in DN patients, diabetic mice and high glucose-exposed cells. Vps34 inhibition impaired lysosomal degradation flux and increased tubular injury markers, ferroptosis, ferritinophagy and CORO1A expression. CORO1A knockdown attenuated ferroptosis and lipid peroxidation, while rescue experiments with Ferrostatin-1 and Erastin confirmed the functional link between CORO1A, vesicular trafficking and ferroptosis. CONCLUSION: CORO1A is elevated in diabetic renal...