title: Claudin-1 regulates pulmonary artery smooth muscle cell proliferation through the activation of ERK1/2.
abstract: Tumor necrosis factor alpha (TNF-α), a crucial inflammatory cytokine, is involved in the pathogenesis of pulmonary arterial hypertension (PAH). TNF-α can induce claudin-1 (CLDN1) expression and CLDN1 has been reported to be associated with the regulation of cellular functions including cell proliferation, migration. Thus, we aimed to explore whether CLDN1 participated in the etiology of PAH. Our study showed that CLDN1 expression was markedly increased in the lungs of rats with monocrotaline(MCT)-induced PAH, especially in the pulmonary arterial smooth muscle sections. We also found that CLDN1 expression in primary human PASMCs was up-regulated by TNF-α, and the Nuclear factor-κB (NF-κB) inhibitor BAY 11-7082 suppressed CLDN1 up-regulation by TNF-a. CLDN1 overexpression by adenoviral transduction promoted PASMCs proliferation, while knockdown of CLDN1 by siRNA inhibited TNF-α-induced cell proliferation. Mechanistic studies revealed that CLDN1 regulated human PASMC proliferation through the activation of ERK1/2. Together, our findings indicate that up-regulation of CLDN1 promotes PASMC proliferation contributing to pulmonary arterial remodeling in PAH.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Xiandong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Huilong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Weining
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China. Electronic address: wangt1616@sina.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D062445:Claudin-1 / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D062445:Claudin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Claudin-1; ERK1/2; NF-κB; Proliferation; Pulmonary arterial hypertension; TNF-α