Previous results have indicated that mitochondrial
ATP-sensitive
potassium (
mitoKATP) channels are associated with the hypoxic proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism underlying the promotive effects of
mitoKATP channels on cell proliferation in response to
hypoxia remains unknown.
mitoKATP channel opening results in a collapse of mitochondrial membrane potential and generation of mitochondrial
reactive oxygen species (ROS). As
hypoxia-inducible factor-1α (HIF-1α) is a critical
oxygen sensor and major transcriptional regulator of the hypoxic adaptive response, the current study assessed whether
mitoKATP opening contributes to the chronic proliferation of human PASMCs (hPASMCs) in collaboration with HIF-1α and its downstream targets under hypoxic conditions. The present study demonstrated that there was crosstalk between
mitoKATP channels and HIF-1α signaling in PASMCs under hypoxic conditions. The results suggest that
mitoKATP channels are involved in the proliferation of PASMCs during
hypoxia through upregulation of the ROS/HIF/
microRNA-210/
iron-
sulfur cluster
protein signaling pathway.