NDLI: Growth differentiation factor 15, a marker of lung involvement in systemic sclerosis, is involved in fibrosis development but is not indispensable for fibrosis development.

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Growth differentiation factor 15, a marker of lung involvement in systemic sclerosis, is involved in fibrosis development but is not indispensable for fibrosis development.

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Year: 2014 Volume: 66 Issue: 1

Growth differentiation factor 15, a marker of lung involvement in systemic sclerosis, is involved in fibrosis development but is not indispensable for fibrosis development.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lambrecht, Stijn Smith, Vanessa De Wilde, Katelijne Coudenys, Julie Decuman, Saskia Deforce, Dieter De Keyser, Filip Elewaut, Dirk
Description	Country affiliation: Belgium Author Affiliation: Lambrecht S ( Ghent University, Ghent, Belgium.)
Abstract	OBJECTIVE: Transforming growth factor ß superfamily members are involved in the pathogenesis of systemic sclerosis (SSc). Growth differentiation factor 15 (GDF-15) is a distant member of this family. We undertook this study to evaluate the role of GDF-15 in SSc pathogenesis. METHODS: A longitudinal prospective cohort of SSc patients was screened for serum GDF-15 levels using enzyme-linked immunosorbent assay, and associations with clinical data were analyzed. In vitro stimulation experiments were performed on lung fibroblasts. The role of GDF-15 in fibrosis development in vivo was evaluated in the bleomycin lung fibrosis model in GDF-15-deficient mice. RESULTS: GDF-15 was measured at baseline in serum samples from 119 SSc patients. An increase in GDF-15 levels was observed in patients classified as having no skin involvement, those with limited cutaneous SSc, and those with diffuse cutaneous SSc. Moreover, baseline serum GDF-15 levels correlated strongly with disease activity and extent of organ involvement, particularly clinical symptoms of lung fibrosis, including impact on lung function at prospective followup. This was mimicked in the bleomycin model of SSc, in which animals exposed to bleomycin had elevated expression levels of GDF-15 in lung tissue. Lung fibroblasts isolated from GDF-15-deficient mice showed reduced induction of interleukin-6 and CCL2 upon bleomycin stimulation. Surprisingly, no differences in fibrosis development were observed between wild-type and GDF-15-deficient animals. CONCLUSION: An intriguing profile of serum GDF-15 levels was found in SSc patients. GDF-15 expression is induced during fibrosis development and markedly correlates with lung function impairment in this disease. The protein may participate in fibrosis initiation, but is not indispensable in the course of fibrosis development in vivo.
File Format	HTM / HTML
ISSN	23265191
Issue Number	2
Volume Number	66
e-ISSN	23265205
Journal	Arthritis & Rheumatology
Language	English
Publisher	Wiley
Publisher Date	2014-02-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Rheumatology Growth Differentiation Factor 15 Metabolism Lung Pathology Pulmonary Fibrosis Scleroderma, Systemic Animals Biological Markers Bleomycin Adverse Effects Pharmacology Chemokine Ccl2 Cohort Studies Comorbidity Disease Models, Animal Fibroblasts Drug Effects Follow-up Studies Deficiency Genetics Humans In Vitro Techniques Interleukin-6 Longitudinal Studies Mice Mice, Knockout Prospective Studies Epidemiology Chemically Induced Skin Diseases Stromal Cells Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology

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