Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.

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 occ...

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Autores principales:	Ling Chen, Qi Ge, Judith L Black, Linhong Deng, Janette K Burgess, Brian G G Oliver
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c676cf90d28b4c5ea686dcd152ddcea5
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spelling	oai:doaj.org-article:c676cf90d28b4c5ea686dcd152ddcea52021-11-18T07:42:36ZDifferential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.1932-620310.1371/journal.pone.0065544https://doaj.org/article/c676cf90d28b4c5ea686dcd152ddcea52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762390/?tool=EBIhttps://doaj.org/toc/1932-6203Fibulin-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 1×10(4) cells/cm(2), 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 µg/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.Ling ChenQi GeJudith L BlackLinhong DengJanette K BurgessBrian G G OliverPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65544 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ling Chen Qi Ge Judith L Black Linhong Deng Janette K Burgess Brian G G Oliver Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.
description	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 1×10(4) cells/cm(2), 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 µg/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.
format	article
author	Ling Chen Qi Ge Judith L Black Linhong Deng Janette K Burgess Brian G G Oliver
author_facet	Ling Chen Qi Ge Judith L Black Linhong Deng Janette K Burgess Brian G G Oliver
author_sort	Ling Chen
title	Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.
title_short	Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.
title_full	Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.
title_fullStr	Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.
title_full_unstemmed	Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.
title_sort	differential regulation of extracellular matrix and soluble fibulin-1 levels by tgf-β₁ in airway smooth muscle cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c676cf90d28b4c5ea686dcd152ddcea5
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_version_	1718423126429138944

Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β₁ in airway smooth muscle cells.

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