title: Periostin mediates cigarette smoke extract-induced proliferation and migration in pulmonary arterial smooth muscle cells.
abstract: Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH). Pulmonary arterial smooth muscle cells (PASMCs) play a critical role in the pathogenesis of PAH-associated arterial remodeling. This study was done to explore the expression and biological roles of periostin in PASMCs following exposure to cigarette smoke extract (CSE). PASMCs were exposed to different concentrations of CSE and tested for gene expression and reactive oxygen species (ROS) production. PASMCs were incubated with recombinant periostin protein or transfected with small interfering RNA targeting periostin before CSE exposure and then examined for cell proliferation and migration. Compared to control cells, exposure to CSE led to a significant upregulation of periostin. Pretreatment with 5mM N-acetyl-l-cysteine (an inhibitor of ROS formation) or 10μM U0126 (an inhibitor of ERK1/2) significantly prevented the induction of periostin in CSE-treated PASMCs. The addition of recombinant periostin protein significantly enhanced the proliferation and migration of PASMCs. In contrast, knockdown of endogenous periostin counteracted the proliferation and migration of PASMCs induced by CSE treatment. In conclusion, CSE induces the expression of periostin in PASMCs via promotion of ROS and activation of ERK1/2. Periostin mediates the effects of CSE on PASMC proliferation and migration. These findings warrant further exploration of the roles of periostin in cigarette smoking-associated pulmonary arterial remodeling.
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Dong-Bo
authors.initials: DB
authors.lastname: Ma
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liu
authors.affiliation: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: drjingwang@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology*; D011651:Pulmonary Artery / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D017382:Reactive Oxygen Species; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cigarette smoke; Migration; Proliferation; Smooth muscle cells; Vascular remodeling