The p-ERK–p-c-Jun–cyclinD1 pathway is involved in proliferation of smooth muscle cells after exposure to cigarette smoke extract

• DOI: 10.1016/j.bbrc.2014.09.062
• Publication Date: 2014-09-28T17:07:57Z
• Authors: Tianjia Li; Ting Song; Leng Ni; Genhuan Yang; Xitao Song; Lifei Wu; Bao Liu; Changwei Liu
• Keywords: Nicotiana; 0303 health sciences; Proto-Oncogene Proteins c-jun; Muscle, Smooth, Vascular; 3. Good health; 03 medical and health sciences; Smoke; Nitriles; Butadienes; Animals; Cyclin D1; Rabbits; Extracellular Signal-Regulated MAP Kinases; Cells, Cultured; Cell Proliferation

An epidemiological survey has shown that smoking is closely related to atherosclerosis, in which excessive proliferation of vascular smooth muscle cells (SMCs) plays a key role. To investigate the mechanism underlying this unusual smoking-induced proliferation, cigarette smoke extract (CSE), prepared as smoke-bubbled phosphate-buffered saline (PBS), was used to induce effects mimicking those exerted by smoking on SMCs. As assessed by Cell Counting Kit-8 detection (an improved MTT assay), SMC viability increased significantly after exposure to CSE. Western blot analysis demonstrated that p-ERK, p-c-Jun, and cyclinD1 expression increased. When p-ERK was inhibited using U0126 (inhibitor of p-ERK), cell viability decreased and the expression of p-c-Jun and cyclinD1 was reduced accordingly, suggesting that p-ERK functions upstream of p-c-Jun and cyclinD1. When a c-Jun over-expression plasmid was transfected into SMCs, the level of cyclinD1 in these cells increased. Moreover, when c-Jun was knocked down by siRNA, cyclinD1 levels decreased. In conclusion, our findings indicate that the p-ERK-p-c-Jun-cyclinD1 pathway is involved in the excessive proliferation of SMCs exposed to CSE.