Hypoxia-inducible factor-1α/β-catenin axis: A conserved regulatory hub for enhancing stem cell function in tissue regeneration

This article provides an in-depth commentary on the study by Wang et al , which elucidates that the hypoxia-inducible factor-1α (HIF-1α)/β-catenin axis serves as a core hub regulating the function of peripheral blood mesenchymal stem cells (PBMSCs) under hypoxic conditions. The research confirms that in a hypoxic environment, HIF-1α acts as an upstream regulator by directly binding to and activating the transcription of β-catenin, a relationship that is unidirectional and irreversible. This axis enhances the therapeutic potential of PBMSCs through a dual mechanism: On one hand, it regulates anti-apoptotic proteins while inhibiting pro-apoptotic molecules, significantly improving cell survival and self-renewal capacity; on the other hand, it promotes the secretion of factors such as vascular endothelial growth factor, thereby enhancing angiogenic activity. In a rat myocardial infarction model, PBMSCs overexpressing HIF-1α showed significantly improved retention in the infarcted area, reduced infarct size, and promoted neovascularization - effects that were abolished upon knockdown of β-catenin. This discovery provides a key target for optimizing stem cell therapy for myocardial infarction. By pre-activating this axis in vitro (e.g., via lentiviral vectors or small-molecule regulators), it is possible to standardize and enhance the survival and reparative capacity of PBMSCs in ischemic tissues, holding important translational medical value.