miR-30e-5p in renal fibrosis: Cross-species multi-model profiling of dynamic networks and clinical prospects.

Abstract

Renal fibrosis is a key pathological process in the progression of chronic kidney disease to end-stage renal disease. However, its underlying mechanisms remain unclear, and there is a lack of effective, early, non-invasive diagnostic markers and specific therapeutic targets. In this study, we constructed a cross-species, multi-model research system to systematically analyze the dynamic expression characteristics of miR-30e-5p and its molecular regulatory mechanism in the different pathological stages of renal fibrosis. We also assessed its clinical translational value. Additionally, the study examined the expression of miR-30e-5p in organs affected by fibrosis. The following was found: 1) miR-30e-5p exhibited distinct expression patterns across injury and fibrosis models. Its expression was upregulated in acute kidney injury but significantly downregulated in various cellular and animal models of renal fibrosis, showing a negative correlation with fibrosis severity. 2) Mechanistic studies indicated that miR-30e-5p inhibits epithelial-mesenchymal transition by targeting Vimentin, thereby attenuating renal fibrosis. 3) Administration of miR-30e-5p agomir ameliorated renal fibrosis in vivo, suggesting its potential as a therapeutic target. 4) In different drug intervention models, the expression level of miR-30e-5p significantly increased after renal fibrosis remission. 5) In different mechanistically induced mouse models of renal fibrosis, the changes in expression of miR-30e-5p in blood, urine, and renal tissues were consistent and significantly decreased. Following pharmacological treatment and agonist intervention, the expression of miR-30e-5p was significantly increased in these body fluids and tissues. This result was also validated in the blood and urine of patients with renal fibrosis. 6) In models of pulmonary, hepatic and myocardial fibrosis, miR-30e-5p expression was significantly down-regulated in tissues and blood, while it was significantly up-regulated in urine. Our results demonstrate that miR-30e-5p attenuates renal fibrosis by targeting Vimentin and may serve as a candidate biomarker for diagnosis and non-invasive monitoring. Its conserved dysregulation in multiple organs also suggests a broader role in fibrotic diseases.