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Differential regulation of extracellular matrix and soluble fibulin-1 Levels by TGF-b1 in airway smooth muscle cells

Citation

Chen, L and Black, JL and Deng, L and Burgess, JK and Oliver, BGG, Differential regulation of extracellular matrix and soluble fibulin-1 Levels by TGF-b1 in airway smooth muscle cells, PLoS One, 8, (6) Article e65544. ISSN 1932-6203 (2013) [Refereed Article]


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Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0) http://creativecommons.org/licenses/by/3.0/

DOI: doi:10.1371/journal.pone.0065544

Abstract

Fibulin-1 (FBLN-1) is a secreted glycoprotein that is associated with extracellular matrix (ECM) formation and rebuilding. Abnormal and exaggerated deposition of ECM proteins is a hallmark of many fibrotic diseases, such as chronic obstructive pulmonary disease (COPD) where small airway fibrosis occurs. The aim of this study was to investigate the regulation of FBLN-1 by transforming growth factor beta 1 (TGF-β1) (a pro-fibrotic stimulus) in primary human airway smooth muscle (ASM) cells from volunteers with and without COPD. Human ASM cells were seeded at a density of 1104 cells/cm2, and stimulated with or without TGF-β1 (10 ng/ml) for 72 hours before FBLN-1 deposition and soluble FBLN-1 were measured. Fold change in FBLN-1 mRNA was measured at 4, 8, 24, 48, 72 hours. In some experiments, cycloheximide (0.5 g/ml) was used to assess the regulation of FBLN-1 production. TGF-β1 decreased the amount of soluble FBLN-1 both from COPD and non-COPD ASM cells. In contrast, the deposition of FBLN-1 into the ECM was increased in ASM cells obtained from both groups. TGF-β1 did not increase FBLN-1 gene expression at any of the time points. There were no differences in the TGF-β1 induced FBLN-1 levels between cells from people with or without COPD. Cycloheximide treatment, which inhibits protein synthesis, decreased both the constitutive release of soluble FBLN-1, and TGF-β1 induced ECM FBLN-1 deposition. Furthermore, in cycloheximide treated cells addition of soluble FBLN-1 resulted in incorporation of FBLN-1 into the ECM. Therefore the increased deposition of FBLN-1 by ASM cells into the ECM following treatment with TGF-β1 is likely due to incorporation of soluble FBLN-1 rather than de-novo synthesis.

Item Details

Item Type:Refereed Article
Keywords:fibulin-1, extracellular matrix, chronic obstructive pulmonary disease, airway smooth muscle, transforming growth factor-beta 1
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
Author:Chen, L (Dr Ling Chen)
ID Code:94863
Year Published:2013
Web of Science® Times Cited:7
Deposited By:Medicine (Discipline)
Deposited On:2014-09-18
Last Modified:2017-11-01
Downloads:534 View Download Statistics

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