miR-206 regulates hypoxia-induced mitophagy and phenotypic remodeling in yak pulmonary artery smooth muscle cells

Hypoxia drives pulmonary artery smooth muscle cells (PASMCs) proliferation and phenotypic remodeling, processes central to vascular adaptation. Yaks, native to high-altitude environments, provide a natural model for studying cellular responses to chronic hypoxia. In this study, hypoxic exposure enhanced yak PASMCs' proliferation and induced phenotypic transformation. Transcriptome profiling revealed that hypoxia suppresses microRNA-206 (miR-206), a regulator of vascular smooth muscle homeostasis. Loss of miR-206 activated the HIF-1α/BNIP3-dependent mitophagy pathway, increased mitophagy levels, and accelerated cell-cycle progression. Restoration of miR-206 reversed these effects, confirming its inhibitory role. Mechanistically, miR-206 directly targets the HIF-1α/BNIP3 signaling axis, linking noncoding RNA regulation to mitochondrial quality control under low oxygen. These findings define a miR-206-HIF-1α/BNIP3 regulatory circuit that coordinates mitophagy and phenotypic remodeling in yak PASMCs. This mechanism highlights the contribution of miRNA-mediated mitochondrial regulation to hypoxia adaptation and offers new insight into pulmonary vascular remodeling in high-altitude mammals.