SIRT3 Upregulation as a Treatment for Lung Fibrosis

In this study, we report that SIRT3 is downregulated in fibroblasts from individuals with idiopathic pulmonary fibrosis and following bleomycin-induced injury in the lungs of aged mice with persistent, non-resolving fibrosis; restoring SIRT3 expression in the late reparative phase reverses established lung fibrosis. Furthermore, this study reveals that the pro-resolution effect of SIRT3 is mediated by macrophage-derived paracrine signaling that activates FOXO3A in fibroblasts, upregulates pro-apoptotic BCL2 family proteins and induces apoptotic cell death essential for fibrosis resolution. Link: https://doi.org/10.1038/s43587-021-00027-5
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