Calcium-sensing receptor mediates hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells through PI3K pathways
LI Guang-wei1,2, LI Bo1, KANG Mei-jia3, XU Fei-xiang1, XING Wen-jing2, XU Chang-qing2,4
1. Department of Pathophysiology, Qiqihar Medical University, Qiqihar 161006, China; 2. Department of Pathophysiology, Harbin Medical University, Harbin 150086, China; 3. Department of Cardiothoracic Surgery, the First Hospital of Qiqihar City, Qiqihar 161006, China; 4. Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086, China
Abstract：AIM:To explore the signal transduction pathways of calcium-sensing receptor(CaSR) that mediates hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells(PASMCs). METHODS:The expression of cyclin D1 and phosphorylated protein kinase B(p-Akt) was analyzed by Western blotting. Cell proliferation was tested using a BrdU incorporation assay, and cell cycle analysis was carried out using a flow cytometric assay. RESULTS:Hypoxia significantly increased the expression of cyclin D1 and p-Akt, the BrdU incorporation and the cell proliferation index. GdCl3, an agonist of CaSR, amplified the effect of hypoxia. LY294002,a PI3K inhibitor, decreased the up-regulation of cyclin D1 expression and the BrdU incorporation, and also inhibited the increase in the cell proliferation index induced by hypoxia and GdCl3 in PASMCs. CONCLUSION: The CaSR mediates hypoxia-induced proliferation of rat PASMCs through PI3K pathways.
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