title: Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts.
abstract: COPD lung is characterized by loss of alveolar elastic fibers and an increase in the chondroitin sulfate (CS) matrix proteoglycan versican V1 (V1). V1 is a known inhibitor of elastic fiber deposition and this study investigates the effects of knockdown of V1, and add-back of CS, on CCL-210 lung fibroblasts treated with cigarette smoke extract (CSE) as a model for COPD. CSE inhibited fibroblast proliferation, viability, tropoelastin synthesis, and elastin deposition, and increased V1 synthesis and secretion. V1 siRNA decreased V1 and constituent CS, did not affect tropoelastin production, but blocked the CSE-induced loss in insoluble elastin. Exogenous CS reduced insoluble elastin, even in the presence of V1 siRNA. These findings confirm that V1 and CS impair the assembly of tropoelastin monomers into insoluble fibers, and further demonstrate that specific knockdown of V1 alleviates the impaired assembly of elastin seen in cultures of pulmonary fibroblasts exposed to CSE, indicating a regulatory role for this protein in the pathophysiology of COPD.
authors.affiliation: Department of Pulmonary Medicine, Huadong Hospital, Fudan University, 221# West Yan'an Road, Jing'an District, Shanghai 200040, China.
authors.forename: Lu-lu
authors.initials: LL
authors.lastname: Xu
authors.affiliation: Department of Pulmonary Medicine, Huadong Hospital, Fudan University, 221# West Yan'an Road, Jing'an District, Shanghai 200040, China.
authors.forename: Yun-tao
authors.initials: YT
authors.lastname: Lu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180# Fenglin Road, Xuhui District, Shanghai 200032, China. Electronic address: zhang.jing@zs-hospital.sh.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology & Clinical Pharmacology, FMHS, Health Promotion, DCHS, Faculty of Social and health Science, Unitec, Private Bag 92019, Auckland, New Zealand.
authors.forename: Lian
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Mervyn J
authors.initials: MJ
authors.lastname: Merrilees
authors.affiliation: Department of Pulmonary Medicine, Huadong Hospital, Fudan University, 221# West Yan'an Road, Jing'an District, Shanghai 200040, China. Electronic address: jmqu0906@163.com.
authors.forename: Jie-ming
authors.initials: JM
authors.lastname: Qu
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D004549:Elastin / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012906:Smoke; D013997:Time Factors; D053675:Versicans / Q000172:deficiency* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012906:Smoke; D053675:Versicans; D002809:Chondroitin Sulfates; D004549:Elastin
keywords: COPD; Elastin; Pulmonary fibroblast; Versican