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

• Published in: The international journal of biochemistry & cell biology Vol. 80; pp. 57 - 65
• Main Authors: Sikora, Anne-Sophie, Hellec, Charles, Carpentier, Mathieu, Martinez, Pierre, Delos, Maxime, Denys, Agnès, Allain, Fabrice
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2016
• Subjects: Cell Line; Fibroblast; Fibroblasts - drug effects; Fibroblasts - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Heparan sulfates; Heparitin Sulfate - metabolism; Humans; Inflammation; Sulf; Sulfotransferases - biosynthesis; Sulfotransferases - genetics; Sulfotransferases - metabolism; Sulfotransferases - secretion; Tumor Necrosis Factor-alpha - pharmacology; 4-MUS; FGF; HRP; CM; Inflammation; HPRT; HS; ECM; AMAC; GlcUA; GlcN; HS6ST; IdoUA; NDST; HS3ST; TNF-α; HS2ST; RT-PCR; FCS; Heparan sulfates; Sulf; Fibroblast
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2016.09.021

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.