Key Laboratory of Pulmonary Diseases of Ministry of Health, Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
J Cell Biochem. 2011 Aug;112(8):2082-8. doi: 10.1002/jcb.23131.
Cigarette smoke could induce pulmonary smooth muscle cells (PASMCs) proliferation. Although our previous study had implied the involvement of protein kinase Cα (PKCα), the molecular mechanism underlying PKCα pathway in this process is still unknown. In this study, rat PASMCs were stimulated by cigarette smoke extract (CSE) or PMA (a special activator to PKCα). Two percent CSE and PMA significantly enhanced cyclin D1 expression and cells proliferation. But cyclin D1-specific siRNA successfully inhibited DNA synthesis in CSE-treated or PMA-treated cells. On the other hand, PKCα-specific siRNA significantly suppressed cyclin D1 expression in CSE-treated cells. Moreover, PKCα-specific siRNA resulted in a cell-cycle arrest in G0/G1 and decreased cells number significantly. We conclude that CSE induced rat PASMCs proliferation at least partly via PKCα-mediated cyclin D1 expression.
香烟烟雾可诱导肺平滑肌细胞(PASMCs)增殖。尽管我们之前的研究提示蛋白激酶 Cα(PKCα)的参与,但该过程中 PKCα 通路的分子机制尚不清楚。在这项研究中,香烟烟雾提取物(CSE)或 PMA(PKCα 的特殊激活剂)刺激大鼠 PASMCs。2% CSE 和 PMA 显著增强了细胞周期蛋白 D1 的表达和细胞增殖。但是,细胞周期蛋白 D1 特异性 siRNA 成功地抑制了 CSE 或 PMA 处理的细胞中的 DNA 合成。另一方面,PKCα 特异性 siRNA 显著抑制了 CSE 处理的细胞中细胞周期蛋白 D1 的表达。此外,PKCα 特异性 siRNA 导致细胞周期停滞在 G0/G1 期,细胞数量明显减少。我们得出结论,CSE 至少部分通过 PKCα 介导的细胞周期蛋白 D1 表达诱导大鼠 PASMCs 增殖。