Inhibition of RELM-β prevents hypoxia-induced overproliferation of human pulmonary artery smooth muscle cells by reversing PLC-mediated KCNK3 decline

Publication date: Available online 8 February 2020Source: Life SciencesAuthor(s): Linlin Han, Nannan Song, Xiaomin Hu, Afang Zhu, Xin Wei, Jinmin Liu, Shiying Yuan, Weike Mao, Xiangdong ChenAbstractAimsAlthough resistin-like molecule β (RELM-β) is involved in the pathological processes of various lung diseases, such as pulmonary inflammation, asthma and fibrosis, its potential roles in hypoxic pulmonary arterial hypertension (PAH) remain largely unknown. The study aims to investigate whether RELM-β contributes to hypoxia-induced excessive proliferation of human pulmonary artery smooth muscle cells (PASMCs) and to explore the potential mechanisms of this process.Main methodsHuman PASMCs were exposed to normoxia or hypoxia (1% O2) for 24 h. siRNA targeting RELM-β was transfected into cells. Protein levels of KCNK3, RELM-β, pSTAT3 and STAT3 were determined by immunoblotting. The translocation of NFATc2 and expression of KCNK3 were visualized by immunofluorescence. 5-ethynyl-2′-deoxyuridine assays and cell counting kit-8 assays were performed to assess the proliferation of PASMCs.Key findings(1) Chronic hypoxia significantly decreased KCNK3 protein levels while upregulating RELM-β protein levels in human PASMCs, which was accompanied by excessive proliferation of cells. (2) RELM-β could promote human PASMCs proliferation and activate the STAT3/NFAT axis by downregulating KCNK3 protein under normoxia. (3) Inhibition of RELM-β expression effectively prevented KCNK3-medi...
Source: Life Sciences - Category: Biology Source Type: research