Xing Ai-ping, Du Yong-cheng, Hu Xiao-yun, Xu Jian-ying, Zhang Huan-ping, Li Yi, Nie Xin
Department of Respiration Medicine, First Hospital, Shanxi Medical University, Taiyuan 030001, China.
J Biomed Biotechnol. 2012;2012:534384. doi: 10.1155/2012/534384. Epub 2012 Jun 11.
Accumulating evidence suggests a direct role for cigarette smoke in pulmonary vascular remodeling, which contributes to the development of pulmonary hypertension. However, the molecular mechanisms underlying this process remain poorly understood. Platelet-derived growth factor (PDGF) is a potential mitogen and chemoattractant implicated in several biological processes, including cell survival, proliferation, and migration. In this study, we investigated the effect of cigarette smoke extract (CSE) on cell proliferation of rat pulmonary artery smooth muscle cells (rPASMCs). We found that stimulation of rPASMCs with CSE significantly increased cell proliferation and promoted cell cycle progression from G1 phase to the S and G2 phases. CSE treatment also significantly upregulated the mRNA and protein levels of PDGFB and PDGFRβ. Our study also revealed that Rottlerin, an inhibitor of PKCδ signaling, prevented CSE-induced cell proliferation, attenuated the increase of S and G2 phase populations induced by CSE treatment, and downregulated PDGFB and PDGFRβ mRNA and protein levels in rPASMCs exposed to CSE. Collectively, our data demonstrated that CSE-induced cell proliferation of rPASMCs involved upregulation of the PKCδ-PDGFB pathway.
越来越多的证据表明，香烟烟雾在肺血管重塑中起直接作用，而肺血管重塑会导致肺动脉高压的发展。然而，这一过程背后的分子机制仍知之甚少。血小板衍生生长因子（PDGF）是一种潜在的促有丝分裂剂和趋化因子，参与包括细胞存活、增殖和迁移在内的多种生物学过程。在本研究中，我们研究了香烟烟雾提取物（CSE）对大鼠肺动脉平滑肌细胞（rPASMCs）细胞增殖的影响。我们发现，用CSE刺激rPASMCs可显著增加细胞增殖，并促进细胞周期从G1期进展到S期和G2期。CSE处理还显著上调了PDGFB和PDGFRβ的mRNA和蛋白水平。我们的研究还表明，PKCδ信号抑制剂rottlerin可阻止CSE诱导的细胞增殖，减弱CSE处理诱导的S期和G2期细胞群的增加，并下调暴露于CSE的rPASMCs中PDGFB和PDGFRβ的mRNA和蛋白水平。总体而言，我们的数据表明，CSE诱导的rPASMCs细胞增殖涉及PKCδ-PDGFB途径的上调。
