{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:11:52Z","timestamp":1783699912506,"version":"3.55.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>The pathogenesis of diabetic nephropathy (DN), a primary microvascular complication of diabetes and a leading cause of end-stage renal disease, remains incompletely understood. This study delved into the role and underlying mechanisms of miR-216a-5p in the development of DN. Our initial findings revealed a lower serum level of miR-216a-5p in DN patients (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). <jats:italic>In vitro<\/jats:italic> experiments, in which high glucose concentrations were used to stimulate human mesangial cells (HMCs), demonstrated a significant increase in the protein level of high mobility group box 1 (HMGB1) and a marked decrease in miR-216a-5p expression (all <jats:italic>P<\/jats:italic> &amp;lt; 0.05). Subsequent cell experiments showed that miR-216a-5p enhanced HMC viability, stimulated cell proliferation and inhibited cell apoptosis. It also alleviated the fibrosis and inflammatory response of HMC cells under high glucose conditions (all <jats:italic>P<\/jats:italic> &amp;lt; 0.05). A dual-luciferase reporter assay confirmed a direct binding between HMGB1 and miR-216a-5p. Moreover, miR-216a-5p suppressed the expression of HMGB1, as well as its receptor for advanced glycation end products (RAGEs). In summary, miR-216a-5p protects against high glucose-induced HMC injury by targeting the HMGB1\/RAGE pathway, providing a new perspective for the subsequent treatment of DN.<\/jats:p>","DOI":"10.3389\/fendo.2025.1669791","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:15:03Z","timestamp":1760415303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["MiR-216a-5p protects against high glucose-induced HMC injury by targeting the HMGB1\/RAGE signaling 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