{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:26:54Z","timestamp":1786688814932,"version":"build-2736575974"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sunitinib is a widely used multi-target tyrosine kinase inhibitor associated with side effects that may impair tissue repair and regeneration, potentially contributing to the onset of medication-related osteonecrosis of the jaw. Macrophages play a central role in tissue homeostasis and regeneration, and their dysfunction may be a key factor in this pathological process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, a zebrafish tail fin injury regeneration model was used to investigate the effects of sunitinib on macrophage function and tissue regeneration. Transcriptomic analysis, immunofluorescence staining, RT-qPCR, and Seahorse mitochondrial stress assays were performed to elucidate the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sunitinib treatment significantly impaired macrophage migration and tissue regeneration in a concentration-dependent manner. Transcriptomic analysis revealed that sunitinib markedly suppressed the PPAR\u03b3 signaling pathway, reparative gene programs, and mitochondrial metabolism. The density of PPAR\u03b3+ macrophages at the wound site was significantly reduced following sunitinib exposure. Treatment with rosiglitazone, a PPAR\u03b3 agonist, effectively rescued the regeneration defects induced by sunitinib, restored macrophage infiltration, and recovered oxidative phosphorylation. Notably, these rescuing effects were abolished upon macrophage depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our results demonstrate that sunitinib impairs tissue regeneration by suppressing PPAR\u03b3 signaling and oxidative phosphorylation in macrophages. Targeting the PPAR\u03b3 pathway represents a promising therapeutic strategy to reverse sunitinib-associated deficits in tissue repair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1900449","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:31:47Z","timestamp":1786685507000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sunitinib induces macrophage dysfunction and impaired tissue regeneration through suppression of PPAR\u03b3"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhouchen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology","place":["Beijing, China"]},{"name":"National Clinical Research Center for Oral Diseases, Peking University School and Hospital of Stomatology","place":["Beijing, China"]},{"name":"National Engineering 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