Prodigiosin protects bone marrow-derived mesenchymal stem cells from hypoxia-induced apoptosis by modulating HIF-1α/YAP-associated signaling

Introduction Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in regenerative medicine, but their poor survival in hypoxic microenvironments limits their therapeutic efficacy. Here, we investigated whether Prodigiosin protects BMSCs against CoCl2-induced hypoxic injury and explored the involvement of HIF-1α/YAP-associated signaling. Methods BMSCs were cultured and phenotyped by flow cytometry. Hypoxia was induced with CoCl (100 μM, 24 h). Cells were treated with Prodigiosin (20 nM) and/or Verteporfin (0.5 μM), or transfected with HIF-1α siRNA. Viability was measured by CCK-8; apoptosis by Annexin V/PI and DAPI; ROS by DHE; and protein expression by Western blot. Data were analyzed by ANOVA or unpaired t-test (P < 0.05). Results and Discussion CoCl2 exposure reduced BMSCs viability, increased apoptosis, promoted reactive oxygen species (ROS) accumulation, and induced HIF-1α expression. These changes were accompanied by a decrease in the p-YAP/YAP ratio and increased expression of Bax and active caspase-3. Prodigiosin treatment alleviated CoCl?-induced cytotoxicity, suppressed ROS accumulation and apoptosis, and partially restored the p-YAP/YAP ratio. In addition, both the YAP inhibitor Verteporfin and HIF-1α knockdown reduced hypoxia-induced apoptosis, supporting the involvement of HIF-1α/YAP-associated signaling in BMSC injury under hypoxic stress. Together, these results suggest that Prodigiosin protects BMSCs from hypoxia-induced apoptosis, at least in part by modulating HIF-1α/YAP-related signaling, and may help improve stem cell survival in hypoxic regenerative environments.