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Sunitinib Induces Macrophage Dysfunction and Impaired Tissue Regeneration Through Suppression of PPARγ

ABSTRACT: Sunitinib, a widely used multi-target tyrosine kinase inhibitor, has side effects that Q6 may impact 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 study, using a zebrafish model, we found that sunitinib treatment impaired macrophage migration and tissue regeneration. Transcriptomic analysis further revealed that sunitinib significantly suppressed the PPARg signaling pathway, reparative gene program and mitochondrial metabolism, confirmed by immunofluorescene staining, RT-qPCR and seahorse mitochondrial stress assays. Treatment with rosiglitazone (PPARg agonist) effectively rescued the regeneration defects induced by sunitinib, an effect that was abolished upon macrophage depletion. Rosiglitazone also recovered the oxidative phosphoryla_x0002_tion in macrophages. Collectively, our results demonstrate that sunitinib impairs tissue regeneration by suppressing PPARg signaling and oxidative phosphorylation in macrophages, and that targeting the PPARg pathway represents a promising therapeutic strategy to reverse sunitinib-associated deficits in tissue repair.

ORGANISM(S): Danio rerio

PROVIDER: GSE342695 | GEO | 2026/08/10

REPOSITORIES: GEO

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