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

Hongling Hu; Yu Ding; Yang Wang; Shuang Geng; Jue Liu; Jinrong He; Yang Lu; Xueying Li; Mingli Yuan; Shan Zhu; Su Zhao

doi:10.3892/etm.2017.5322

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

Exp Ther Med. 2017 Dec;14(6):6105-6112. doi: 10.3892/etm.2017.5322. Epub 2017 Oct 17.

Authors

Hongling Hu¹, Yu Ding^{2

3}, Yang Wang¹, Shuang Geng¹, Jue Liu⁴, Jinrong He^{2

3}, Yang Lu¹, Xueying Li¹, Mingli Yuan¹, Shan Zhu¹, Su Zhao¹

Affiliations

¹ Department of Respiratory Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
² Key Laboratory for Molecular Diagnosis of Hubei, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
³ Central Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
⁴ Department of Clinical Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.

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.

Keywords: hypoxia; hypoxia-inducible factor-1α; iron-sulfur cluster protein; microRNA-210; mitochondrial ATP-sensitive potassium channel; mitochondrial membrane potential; pulmonary artery smooth muscle cells.