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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.
AuthorsLu-lu Xu, Yun-tao Lu, Jing Zhang, Lian Wu, Mervyn J Merrilees, Jie-ming Qu
JournalRespiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 215 Pg. 58-63 (Aug 15 2015) ISSN: 1878-1519 [Electronic] Netherlands
PMID25999281 (Publication Type: Journal Article)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • RNA, Messenger
  • RNA, Small Interfering
  • Smoke
  • Versicans
  • Chondroitin Sulfates
  • Elastin
Topics
  • Cell Proliferation (drug effects, physiology)
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Chondroitin Sulfates (metabolism)
  • Elastin (metabolism)
  • Fibroblasts (drug effects)
  • Gene Expression Regulation (drug effects, physiology)
  • Humans
  • Lung (cytology)
  • RNA, Messenger (metabolism)
  • RNA, Small Interfering (pharmacology)
  • Smoke
  • Time Factors
  • Versicans (deficiency, genetics)

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