Tumour-necrosis factor-α induces heparan sulfate 6-O-endosulfatase 1 (Sulf-1) expression in fibroblasts.
Int J Biochem Cell Biol
; 80: 57-65, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27693418
ABSTRACT
Heparan sulfate (HS) 6-O-endosulfatases (Sulfs) have emerged recently as critical regulators of many physiological and pathological processes. By removing 6-O-sulfates from specific HS sequences, they modulate the activities of a variety of growth factors and morphogens, including fibroblast growth factor (FGF)-1. However, little is known about the functions of Sulfs in inflammation. Tumour-necrosis factor (TNF)-α plays an important role in regulating the behaviour of fibroblasts. In this study, we examined the effect of this inflammatory cytokine on the expression of Sulfs in human MRC-5 fibroblasts. Compositional analysis of HS from TNF-α-treated cells showed a strong reduction in the amount of the trisulfated UA2S-GlcNS6S disaccharide, which suggested a selective reaction of 6-O-desulfation. Real-time PCR analysis revealed that TNF-α increased Sulf-1 expression in a dose- and time-dependent manner, via a mechanism involving NF-ĸB, ERK1/2 and p38 MAPK. In addition, we confirmed that cell stimulation with TNF-α was accompanied by the secretion of an active form of Sulf-1. To study the function of Sulf- 1, we examined the responses induced by FGF-1. We showed that ERK1/2 activation and cell proliferation were markedly reduced in TNF-α-treated MRC-5 cells compared with untreated cells. Silencing the expression of Sulf-1 by RNA interference restored the responses induced by FGF-1, which indicated that TNF-α-mediated induction of the sulfatase indeed resulted in alterations of HS biological properties. Taken together, our results indicate that Sulf-1 is responsive to TNF-α stimulation and may function as an autocrine regulator of fibroblast expansion in the course of an inflammatory response.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfotransferases
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Regulação Enzimológica da Expressão Gênica
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Fator de Necrose Tumoral alfa
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Fibroblastos
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Heparitina Sulfato
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article