title: Deposition of insoluble elastin by pulmonary fibroblasts from patients with COPD is increased by treatment with versican siRNA.
abstract: A reduced content of alveolar elastic fibers is a key feature of COPD lung. Despite continued elastogenic potential by alveolar fibroblasts in the lung affected by COPD, repair of elastic fibers does not take place, which is due to increased levels of the chondroitin sulfate proteoglycan versican that inhibits the assembly of tropoelastin into fibers. In this study, primary pulmonary fibroblast cell lines from COPD and non-COPD patients were treated with a small interfering RNA (siRNA) against versican to determine if knockdown of versican could restore the deposition of insoluble elastin. Versican siRNA treatment reduced versican expression and secretion by pulmonary fibroblasts from both COPD and non-COPD patients (P<0.01) and significantly increased deposition of insoluble elastin in the COPD cell cultures (P<0.05). The treatment, however, did not significantly affect production of soluble elastin (tropoelastin) in either the COPD or non-COPD cell cultures, supporting a role for versican in inhibiting assembly but not synthesis of tropoelastin. These results suggest that removal or knockdown of versican may be a possible therapeutic strategy for increasing deposition of insoluble elastin and stimulating repair of elastic fibers in COPD lung.
authors.affiliation: Department of Community and Health Services, Unitec; Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand.
authors.forename: Lian
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jie Ming
authors.initials: JM
authors.lastname: Qu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University.
authors.forename: Chun-Xue
authors.initials: CX
authors.lastname: Bai
authors.affiliation: Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
authors.forename: Mervyn J
authors.initials: MJ
authors.lastname: Merrilees
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D015536:Down-Regulation; D004549:Elastin / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods*; D012995:Solubility; D013997:Time Factors; D014162:Transfection; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism; D053675:Versicans / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D014333:Tropoelastin; C508322:VCAN protein, human; D053675:Versicans; D004549:Elastin
keywords: COPD; elastin; pulmonary fibroblasts; versican