{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:18:43Z","timestamp":1792034323668,"version":"4.4.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"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. Immunol."],"abstract":"<jats:p>Cisplatin is a chemotherapy drug used to treat different solid tumors, including ovarian, bladder, lung, and head and neck cancers. One of its significant side effects is ototoxicity, especially when high doses are required. Cisplatin-induced ototoxicity is associated with increased cochlear cell death resulting from DNA damage, caspase activation, oxidative stress, inflammation, and glutamate excitotoxicity. The regulator of G protein signaling 17 (RGS17), a member of the RGS-RZ subfamily, hastens the hydrolysis of GTP to GDP on the G<jats:sub>\u03b1<\/jats:sub> subunit. In the current study, we demonstrate the role of <jats:italic>RGS17<\/jats:italic> in cisplatin-induced cochlear inflammation and ototoxicity. C57BL\/6J mice treated with two cycles of cisplatin (3.5 mg\/kg) showed a significant elevation in ABR thresholds, along with loss of outer hair cells and inner hair cells synapse. Furthermore, immunohistochemical analysis revealed that cisplatin administration upregulates CXCL1, accompanied by an increase in the number of CD45 and CD68-positive immune cells. On the other hand, <jats:italic>RGS17<\/jats:italic> knockout in hair cells protects against cisplatin-induced elevation of ABR thresholds, outer hair cell loss, cochlear inflammation, and inner hair cell synaptopathy. Moreover, <jats:italic>RGS17<\/jats:italic> knockout downregulates CXCL1 immunolabeling and decreases the number of CD45 and CD68-positive immune cells induced by cisplatin. These results suggest that <jats:italic>RGS17<\/jats:italic> is implicated in cisplatin ototoxicity, potentially by initiating the immune cascade, and indicate <jats:italic>RGS17<\/jats:italic> as a relevant target for treating cisplatin ototoxicity.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1470625","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T05:19:50Z","timestamp":1740115190000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of RGS17 in cisplatin-induced cochlear inflammation and ototoxicity via caspase-3 activation"],"prefix":"10.3389","volume":"16","author":[{"given":"Raheem F. H.","family":"Al Aameri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Entkhab M. 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