title: Cigarette smoke extract induces apoptosis of rat alveolar Type II cells via the PLTP/TGF-β1/Smad2 pathway.
abstract: Apoptosis of alveolar epithelial cells has been implicated in the pathogenesis of acute lung injury. Phospholipid transfer protein (PLTP) may play a role in apoptosis. In the present study, the effect of the novel function of PLTP in cigarette smoke extract (CSE)-induced apoptosis of alveolar epithelial cells and the possible mechanism were examined. Male Wistar rats were exposed to air and cigarette smoke (n=10/exposure) for 6h/day on 3 consecutive days, then the lungs were sectioned and examined. To investigate effects on alveolar epithelial cells, rat alveolar epithelial cells (RLE-6TN) were treated with different concentrations of CSE for various times. siRNA for PLTP was transfected into cells and an inhibitor of the transforming growth factor-β1 (TGF-β1) type I receptor was administered prior to CSE exposure. Apoptosis was measured, and mRNA expression of PLTP and TGF-β1 and protein levels of PLTP, TGF-β1, p-Smad2 and cleaved caspase-3 were analyzed. The results showed that apoptosis, as well as expression of PLTP, TGF-β1, p-Smad2 and cleaved caspase-3 were all significantly increased after CSE stimulation (P<0.05). Furthermore, the expression of TGF-β1, p-Smad2 and cleaved caspase-3 induced by CSE could be partly abrogated by knockdown of PLTP. The expression of PLTP showed no significant change as a result of TGF-β1 receptor inhibition, while cleaved caspase-3 showed a remarkable reduction. PLTP may act as an upstream signal molecule of the TGF-β1/Smad2 pathway and is likely to be involved in CSE-induced apoptosis of alveolar epithelial cells.
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: hopehong2003@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Respiratory Department, Chengdu Seventh People's Hospital, Chengdu, China. Electronic address: keliaocqmu@sina.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Liao
authors.affiliation: Drug Engineering Research Center of Chongqing Medical University, Chongqing, China. Electronic address: 467202699@qq.com.
authors.forename: Lv
authors.initials: L
authors.lastname: Cui-Zhao
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China. Electronic address: wenfuqiang@126.com.
authors.forename: Fu
authors.initials: F
authors.lastname: Qiang-Wen
authors.affiliation: Respiratory Department, The Third People's Hospital of Cheng Du, Cheng Du, China. Electronic address: zengxf825@sohu.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Feng-Zeng
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 790612391@qq.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Ping-Wu
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: GUOSL999@sina.com.
authors.forename: Shu
authors.initials: S
authors.lastname: Liang-Guo
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Juan-Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D008297:Male; D049294:Phospholipid Transfer Proteins / Q000276:immunology / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein / Q000276:immunology / Q000378:metabolism*; D012906:Smoke; D012907:Smoking / Q000009:adverse effects*; D062789:Tobacco Products / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism*
chemical_list: D049294:Phospholipid Transfer Proteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D012906:Smoke; D053773:Transforming Growth Factor beta1
keywords: Alveolar Type II cells; Apoptosis; Cigarette smoke extract; Phospholipid transfer protein; Smad2; Transforming growth factor-β1