Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
J Cell Biochem. 2012 Jan;113(1):349-59. doi: 10.1002/jcb.23361.
Cigarette smoke has been demonstrated to induce pulmonary vascular remodeling, which is characterized by medial thickening of the pulmonary arteries mainly resulting from the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the molecular mechanism underlying this process is still unclear. In the present study, we investigated whether CCN2 regulated rat PASMCs (rPASMCs) proliferation induced by cigarette smoke extract (CSE) and nicotine by upregulating cyclin D1 in vitro. CCN2 siRNA or cyclin D1 siRNA were transfected to rPASMCs which were then exposed to CSE and nicotine. Both mRNA and protein expressions of CCN2 were significantly increased in rPASMCs treated with 2% CSE or 1 µM nicotine, which markedly promoted the proliferation of rPASMCs. CCN2 siRNA inhibited the proliferation of rPASMCs induced by CSE or nicotine. Furthermore, CCN2 siRNA markedly suppressed the mRNA and protein expressions of cyclin D1 in rPASMCs and led to cell cycle arrest in G0/G1 phase resulting in reduced rPASMCs proliferation. These findings suggest that CCN2 contributes to the CSE and nicotine-induced proliferation of rPASMCs at least in part by upregulating cyclin D1 expression.
香烟烟雾已被证实可诱导肺血管重构，其特征为肺小动脉中层增厚，主要由肺动脉平滑肌细胞（PASMCs）的异常增殖所致。然而，这一过程的分子机制仍不清楚。本研究通过上调细胞周期蛋白 D1（cyclin D1），探讨了结缔组织生长因子 2（CCN2）是否调控香烟烟雾提取物（CSE）和尼古丁诱导的大鼠 PASMCs（rPASMCs）增殖。将 CCN2 siRNA 或 cyclin D1 siRNA 转染至 rPASMCs，然后用 CSE 和尼古丁进行处理。结果发现，2% CSE 或 1µM 尼古丁处理的 rPASMCs 中 CCN2 的 mRNA 和蛋白表达明显增加，明显促进了 rPASMCs 的增殖。CCN2 siRNA 抑制了 CSE 或尼古丁诱导的 rPASMCs 增殖。此外，CCN2 siRNA 明显抑制了 rPASMCs 中 cyclin D1 的 mRNA 和蛋白表达，导致细胞周期停滞在 G0/G1 期，从而减少 rPASMCs 的增殖。这些发现表明，CCN2 通过上调 cyclin D1 的表达，至少部分促进了 CSE 和尼古丁诱导的 rPASMCs 增殖。
