title: The p-ERK-p-c-Jun-cyclinD1 pathway is involved in proliferation of smooth muscle cells after exposure to cigarette smoke extract.
abstract: 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.
authors.affiliation: Department of Vascular surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Tianjia
authors.initials: T
authors.lastname: Li
authors.affiliation: Nursing Department of Orthopedics 3rd Ward, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Vascular surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Leng
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Vascular surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Genhuan
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Vascular surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Xitao
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Vascular surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Vascular surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China. Electronic address: liubao72@yahoo.com.cn.
authors.forename: Bao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Vascular surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China. Electronic address: liucw@vip.sina.com.
authors.forename: Changwei
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011817:Rabbits; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D002070:Butadienes; D009570:Nitriles; D016755:Proto-Oncogene Proteins c-jun; D012906:Smoke; C113580:U 0126; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cigarette smoke extract; CyclinD1; ERK; Smooth muscle cell proliferation; c-Jun