Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts
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Other Title
Authors
Xu, Lulu
Lu, Yuntao
Zhang, Jing
Wu, Lian
Merrilees, Mervyn J.
Qu, J.
Lu, Yuntao
Zhang, Jing
Wu, Lian
Merrilees, Mervyn J.
Qu, J.
Author ORCID Profiles (clickable)
Degree
Grantor
Date
2015-05-11
Supervisors
Type
Journal Article
Ngā Upoko Tukutuku (Māori subject headings)
Keyword
pulmonary fibroblast
COPD
elastin
versican
chronic obstructive pulmonary disease (COPD)
COPD
elastin
versican
chronic obstructive pulmonary disease (COPD)
ANZSRC Field of Research Code (2020)
Citation
Xu, L., Lu, Y., Zhang, J., Wu, L., Merrilees, M., & Qu, J. (2015). Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts. Respiratory Physiology & Neurobiology, 2015, pp.1-21. doi:doi:10.1016/j.resp.2015.05.004
Abstract
COPD lung is characterized by loss of alveolar elastic fibers and an increase in the chondroitin sulfate (CS) matrix proteoglycan versican 1 (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.
Publisher
Elsevier
Permanent link
Link to ePress publication
DOI
doi:10.1016/j.resp.2015.05.004
Copyright holder
Elsevier
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