MitoKATP channels promote the proliferation of hypoxic human pulmonary artery smooth muscle cells via the ROS/HIF/miR‑210/ISCU signaling pathway

Abstract

Previous results have indicated that mitochondrial ATP-sensitive potassium (mitoK_ATP) channels are associated with the hypoxic proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism underlying the promotive effects of mitoK_ATP channels on cell proliferation in response to hypoxia remains unknown. mitoK_ATP 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 mitoK_ATP 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 mitoK_ATP channels and HIF-1α signaling in PASMCs under hypoxic conditions. The results suggest that mitoK_ATP channels are involved in the proliferation of PASMCs during hypoxia through upregulation of the ROS/HIF/microRNA-210/iron-sulfur cluster protein signaling pathway.