CCN2 promotes cigarette smoke-induced proliferation of rat pulmonary artery smooth muscle cells through upregulating cyclin D1 expression.

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.