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Zool."],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute kidney injury (AKI) is characterized by high incidence and mortality rates, and a lack of specific targeted therapies. Inflammatory responses mediated by immune cells and direct damage to renal tubular epithelial cells underlie AKI development. Melanocortin exerts renoprotective effects through systemic immune regulation; however, the renoprotective role of melanocortin 1 receptor (MC1R) remains unclear. MC1R\u2010deficient (e\/e) mice developed higher serum creatinine levels, more severe renal dysfunction, and greater histological damage than wild\u2010type (WT) mice following folic acid\u2010induced AKI. Treatment with MC1R agonist MS05 improved experimental nephritis in WT mice; however, this effect was less pronounced in e\/e mice. The exacerbation of AKI in e\/e mice was associated with damage to renal tubular epithelial cells and macrophage infiltration, where MC1R is highly expressed. MC1R alleviates tubular cell inflammation by inhibiting the nuclear factor\u2010\u03baB pathway and suppresses the polarization of M1 macrophages. Chimeric mice were generated through transplantation of bone marrow\u2010derived macrophages after irradiation. Macrophages from e\/e mice with MC1R dysfunction exacerbated kidney injury in WT mice, whereas those from WT mice mitigated kidney injury in e\/e mice. Targeting MC1R in renal tubular epithelial cells and macrophages provides a novel treatment concept for AKI.<\/jats:p>","DOI":"10.1111\/1749-4877.70113","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T18:26:53Z","timestamp":1776882413000},"page":"1173-1189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melanocortin 1 Receptor Signaling Protects Against Tubular Epithelial Cell Injury and M1 Macrophage Polarization in Acute Kidney Injury"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8761-4672","authenticated-orcid":false,"given":"Zhan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology Zhengzhou University  Zhengzhou P. R. 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