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• W3006273690 startingPage "117419" @default.
• W3006273690 abstract "Although 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. Human 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. (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-mediated cell proliferation under hypoxia. (4) Phospholipase C (PLC) inhibitor U-73122 could not only prevent the hypoxia/RELM-β-induced decrease in KCNK3 protein, but also inhibit the enhanced cell viability caused by hypoxia/RELM-β. (5) Both hypoxia and RELM-β could downregulate membrane KCNK3 protein levels by enhancing endocytosis. RELM-β activation is responsible for hypoxia-induced excessive proliferation of human PASMCs. Interfering with RELM-β may alleviate the progression of hypoxic PAH by upregulating PLC-dependent KCNK3 expression." @default.
• W3006273690 created "2020-02-24" @default.
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• W3006273690 date "2020-04-01" @default.
• W3006273690 modified "2023-10-15" @default.
• W3006273690 title "Inhibition of RELM-β prevents hypoxia-induced overproliferation of human pulmonary artery smooth muscle cells by reversing PLC-mediated KCNK3 decline" @default.
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• W3006273690 doi "https://doi.org/10.1016/j.lfs.2020.117419" @default.
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