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. (C) 2015 Elsevier B.V. All rights reserved.
[1]Fudan Univ, Huadong Hosp, Dept Pulm Med, Shanghai 200040, Peoples R China.
[2]Fudan Univ, Zhongshan Hosp, Dept Pulm Med, Shanghai 200032, Peoples R China.
[3]Unitec, Fac Social & Hlth Sci, DCHS, Dept Pharmacol & Clin Pharmacol,FMHS,Hlth Promot, Auckland, New Zealand.
[4]Univ Auckland, Fac Med & Hlth Sci, Dept Anat Radiol, Auckland 1, New Zealand.
(8.0+极速模式)