Bleomycin A5 suppresses Drp1-mediated mitochondrial fission and induces apoptosis in human nasal polyp-derived fibroblasts

Intralesional injection of bleomycin-A5 (BLE-A5) is a novel treatment for nasal polyps. Our previous study clarified that BLE-A5 could induce nasal polyp-derived fibroblast (NPDF) apoptosis in nasal polyps. However, the detailed mechanisms are still unclear. The present study aimed to determine the effects of BLE-A5 on NPDF mitochondrial dynamics and provide a theoretical basis for the local application of BLE-A5 to treat nasal polyps. In the present study, an in vitro nasal polyp tissue culture model was used to define the BLE-A5 target cell type in nasal polyps. NPDF primary cell culture was used to study the effects of BLE-A5 on the mitochondrial dynamic-related mechanism. The results showed that BLE-A5 treatment of NPDFs caused mitochondrial-mediated apoptosis. Dynamin-related protein 1 (Drp1) was shown to be altered in BLE-A5-treated NPDFs. Drp1 knockdown increased the sensitivity of NPDFs to BLE-A5 and exacerbated mitochondrial dysfunction. BLE-A5 decreased cyclin B1-CDK1 complex-mediated phosphorylation of Drp1 and inhibited Drp1-mediated mitophagy in NPDFs. Overall, the present study concluded that BLE-A5 mainly induces NPDF apoptosis in nasal polyps. BLE-A5 regulates the mitochondria by inhibiting Drp1 activation, resulting in NPDF mitochondrial dynamic disorder and apoptosis.