title: Cigarette smoke extract stimulates rat pulmonary artery smooth muscle cell proliferation via PKC-PDGFB signaling.
abstract: 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.
authors: Department of Respiration Medicine, First Hospital, Shanxi Medical University, Taiyuan 030001, China.
authors: Ai-ping
authors: AP
authors: Xing
authors: Yong-cheng
authors: YC
authors: Du
authors: Xiao-yun
authors: XY
authors: Hu
authors: Jian-ying
authors: JY
authors: Xu
authors: Huan-ping
authors: HP
authors: Zhang
authors: Yi
authors: Y
authors: Li
authors: Xin
authors: X
authors: Nie
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke; D012907:Smoking; D062789:Tobacco Products
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D020574:Proto-Oncogene Proteins c-sis; D012906:Smoke; C085746:rottlerin; D020797:Receptor, Platelet-Derived Growth Factor beta; D051745:Protein Kinase C-delta