Vascular endothelial injury is a critical driver of renal dysfunction and glomerulosclerosis in chronic kidney disease (CKD). While endothelial damage-induced inflammation contributes to sclerosis, the underlying mechanisms remain unclear. Although miR-214 has been implicated in renal fibrosis, its role in vascular endothelial cells during glomerulosclerosis is undefined. Here, we observed significant miR-214 upregulation in renal endothelial cells of 5/6 nephrectomy (5/6Nx) mice. Endothelial-specific knockout of miR-214 aggravated glomerulosclerosis and endothelial dysfunction, whereas smooth muscle-specific knockout showed no effect. Transcriptome analysis revealed that miR-214 inhibition altered the NF-κB pathway, specifically upregulating RELA. Bioinformatic prediction and luciferase reporter assays confirmed miR-214 directly targets the 3′-UTR of RELA. Modulating miR-214 levels correspondingly regulated RELA expression and activity, and cytokine profiling confirmed that miR-214 suppression enhances pro-inflammatory secretion. Collectively, these results demonstrate that endothelial miR-214 protects against glomerulosclerosis by inhibiting RELA-mediated inflammation, highlighting its potential as a therapeutic target for CKD-related glomerular injury.
Tan et al. (2026) studied this question.