Chronic hypoxia promoted pulmonary arterial smooth muscle cells proliferation through upregulated calcium‐sensing receptorcanonical transient receptor potential 1/6 pathway

• DOI: 10.1111/micc.12715
• Publication Date: 2021-05-19T11:51:08Z
• Authors: Juan Xu; Xing Wen; Zhenli Fu; Yongliang Jiang; Wei Hong; Rongmin Liu; Shaoxing Li; Weitao Cao; Jinding Pu; Lingmei Huang; Bing Li; Pixin Ran; Gongyong Peng
• Keywords: Viability assay; TRPC6

Although both calcium-sensing receptor (CaSR) and canonical transient potential (TRPC) proteins contribute to chronic hypoxia (CH)-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation, the relationship between CaSR TRPC in hypoxic PASMCs proliferation remains poorly understood. The goal of this study was identify that CH promotes through CaSR-TRPC pathway.Rat were isolated treated with CH. Cell assessed by cell counting, CCK-8 assay, EdU incorporation. expressions determined qPCR Western blotting. Store-operated Ca2+ entry (SOCE) extracellular restoration.In PASMCs, enhanced number, viability DNA synthesis, which is accompanied upregulated expression CaSR, TRPC1 TRPC6. Negative modulators (NPS2143, NPS2390) inhibited, whereas positive (spermine, R568) enhanced, CH-induced increases synthesis PASMCs. Knockdown siRNA inhibited upregulation TRPC6 enhancement SOCE attenuated enhancements However, neither siTRPC1 nor siTRPC6 had an effect on upregulation, although significantly PASMCs.These results demonstrate CaSR-TRPC1/6 pathway mediating important pathogenic mechanism under conditions.