Hu Hongling, Ding Yu, Wang Yang, Geng Shuang, Liu Jue, He Jinrong, Lu Yang, Li Xueying, Yuan Mingli, Zhu Shan, Zhao Su
Department of Respiratory Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
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.
Exp Ther Med. 2017 Dec;14(6):6105-6112. doi: 10.3892/etm.2017.5322. Epub 2017 Oct 17.
Previous results have indicated that mitochondrial ATP-sensitive potassium (mitoK) channels are associated with the hypoxic proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism underlying the promotive effects of mitoK channels on cell proliferation in response to hypoxia remains unknown. mitoK 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 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 channels and HIF-1α signaling in PASMCs under hypoxic conditions. The results suggest that mitoK channels are involved in the proliferation of PASMCs during hypoxia through upregulation of the ROS/HIF/microRNA-210/iron-sulfur cluster protein signaling pathway.
先前的研究结果表明，线粒体ATP敏感性钾（mitoK）通道与肺动脉平滑肌细胞（PASMCs）的缺氧增殖有关。然而，mitoK通道在缺氧条件下促进细胞增殖的潜在机制仍不清楚。mitoK通道开放会导致线粒体膜电位崩溃并产生线粒体活性氧（ROS）。由于缺氧诱导因子-1α（HIF-1α）是一种关键的氧传感器和缺氧适应性反应的主要转录调节因子，因此本研究评估了在缺氧条件下，mitoK通道开放是否与HIF-1α及其下游靶点协同作用，促进人PASMCs（hPASMCs）的慢性增殖。本研究表明，在缺氧条件下，PASMCs中的mitoK通道与HIF-1α信号通路之间存在相互作用。结果表明，mitoK通道通过上调ROS/HIF/微小RNA-210/铁硫簇蛋白信号通路，参与缺氧期间PASMCs的增殖。
