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Frontiers of antifibrotic therapy in systemic sclerosis

Distler, JH; Feghali-Bostwick, C; Soare, A; Asano, Y; Distler, O; Abraham, DJ; (2017) Frontiers of antifibrotic therapy in systemic sclerosis. Arthritis & Rheumatology , 69 (2) pp. 257-267. 10.1002/art.39865. Green open access

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Abstract

Although fibrosis is becoming increasingly recognized as a major cause of morbidity and mortality in modern societies, targeted anti-fibrotic therapies are still not approved for most fibrotic disorders. However, intense research over the last decade has improved our understanding of the underlying pathogenesis of fibrotic diseases. We now appreciate fibrosis as the consequence of a persistent tissue repair responses, which, in contrast to normal wound healing, fails to be effectively terminated. Profibrotic mediators released from infiltrating leukocytes, activated endothelial cells and degranulated platelets may predominantly drive fibroblast activation and collagen release in early stages, whereas endogenous activation of fibroblasts due epigenetic modifications and biomechanical or physical factors such as stiffening of the extracellular matrix and hypoxia may play pivotal role for disease progression in later stages. In the present review, we discuss novel insights into the pathogenesis of fibrotic diseases using systemic sclerosis (SSc) as example for an idiopathic, multisystem disorder. We set a strong translational focus and predominantly discuss approaches with very high potential for rapid transfer from bench-to-bedside. We highlight the molecular basis for ongoing clinical trials in SSc and also provide an outlook on upcoming trials. This article is protected by copyright. All rights reserved.

Type: Article
Title: Frontiers of antifibrotic therapy in systemic sclerosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/art.39865
Publisher version: http://doi.org/10.1002/art.39865
Language: English
Additional information: © 2016 American College of Rheumatology. This is the peer reviewed version of the following article: Distler, JH; Feghali-Bostwick, C; Soare, A; Asano, Y; Distler, O; Abraham, DJ; (2016) Frontiers of antifibrotic therapy in systemic sclerosis. Arthritis & Rheumatology 10.1002/art.39865, which has been published in final form at http://dx.doi.org/10.1002/art.39865. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1516175
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