Cell density-dependent stimulation of PAI-1 and hyaluronan synthesis by TGF-ß in orbital fibroblasts.
J Endocrinol
; 229(2): 187-96, 2016 05.
Article
em En
| MEDLINE
| ID: mdl-26979769
ABSTRACT
During the course of Graves' orbitopathy (GO), orbital fibroblasts are exposed to factors that lead to proliferation and extracellular matrix (ECM) overproduction. Increased levels of tissue plasminogen activator inhibitor type 1 (PAI-1 (SERPINE1)) might promote the accumulation of ECM components. PAI-1 expression is regulated by cell density and various cytokines and growth factors including transforming growth factorß(TGF-ß). We examined the effects of increasing cell densities and TGF-ß on orbital fibroblasts obtained from GO patients and controls. Responses were evaluated by the measurement of proliferation, PAI-1 expression, and ECM production. There was an inverse correlation between cell density and the per cell production of PAI-1. GO orbital, normal orbital, and dermal fibroblasts behaved similarly in this respect. Proliferation rate also declined with increasing cell densities. Hyaluronan (HA) production was constant throughout the cell densities tested in all cell lines. In both GO and normal orbital fibroblasts, but not in dermal fibroblasts, TGF-ß stimulated PAI-1 production in a cell density-dependent manner, reaching up to a five-fold increase above baseline. This has been accompanied by increased HA secretion and pericellular HA levels at high cell densities. Increasing cell density is a negative regulator of proliferation and PAI-1 secretion both in normal and GO orbital fibroblasts; these negative regulatory effects are partially reversed in the presence of TGF-ß. Cell density-dependent regulation of PAI-1 expression in the orbit, together with the local cytokine environment, may have a regulatory role in the turnover of the orbital ECM and may contribute to the expansion of orbital soft tissue in GO.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Órbita
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Inibidor 1 de Ativador de Plasminogênio
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Oftalmopatia de Graves
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Fator de Crescimento Transformador beta1
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Ácido Hialurônico
Limite:
Humans
Idioma:
En
Revista:
J Endocrinol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Hungria