Tumour-necrosis factor-α induces heparan sulfate 6-O-endosulfatase 1 (Sulf-1) expression in fibroblasts

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• 作者：Anne-Sophie Sikora¹ ; Charles Hellec ; Mathieu Carpentier ; Pierre Martinez² ; Maxime Delos ; Agnè ; s Denys ; Fabrice Allain ; ^{fabrice.allain@univ-lille1.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：4-MUS ; 4-methylumbelliferyl sulfate ; AMAC ; 2-aminoacridone ; CM ; conditioned medium ; ECM ; extracellular matrix ; FCS ; fetal calf serum ; FGF ; fibroblast growth factor ; GlcUA ; glucuronic acid ; GlcN ; glucosamine ; HPRT ; hypoxanthine-guanine phosphoribosyl transferase ; HRP ; horseradish peroxidase ; HS ; heparan sulfate ; HS2ST ; HS 2-O-sulfotransferase ; HS3ST ; HS 3-O-sulfotransferase ; HS6ST ; HS 6-O-sulfotransferase ; IdoUA ; iduronic acid ; NDST ; N-deacetylase/N-sulfotransferase ; RT-PCR ; reverse transcription
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：80
• 期：Complete
• 页码：57-65
• 全文大小：1075 K

文摘

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.