Understanding Fibrosis in Systemic Sclerosis: Novel and Emerging Treatment Approaches
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SCLERODERMA (J VARGA, SECTION EDITOR)
Understanding Fibrosis in Systemic Sclerosis: Novel and Emerging Treatment Approaches Hanlin Yin 1 & Rui Li 1 & Liangjing Lu 1 & Qingran Yan 1 Accepted: 4 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of the Review Over the years, our perceptions of fibrogenesis in systemic sclerosis (SSc) have advanced a lot. Herein, we review potential targets for SSc discovered in the past 3 years. Recent Findings In recent years, metabolites have come into the limelight of SSc research. Anti-oxidants, promotor of adipogenesis, modulator of fatty acid metabolism, regulator of glucose homeostasis, and adenosine deaminase open a new door for SSc treatment. A mosaic of biolipids, especially cannabinoid receptor 2 agonist, represents a rational therapeutic approach in fibrosis. In terms of immune aspects, targeting chemokines or integrins for cell adhesion may become new approach to inhibiting fibrotic pathways. Epigenetic modulation of immune pathways has been uncovered much recently. Targeting histone modifications and lncRNAs has demonstrated therapeutic potential in SSc animal models. The classical JAK-STAT and interferon pathway drive great attention these years because of the promising potential for the drug repurposing of targeted therapies from arthritis to SSc. In fibrosis-associated developmental pathways, BMP, Hedgehog, and PU.1 are expected to offer new targets to restrain fibrosis. Summary New targets involved in metabolic reprogramming, immunity, epigenetics together with developmental and apoptotic pathways open new avenues for therapeutic modulation in SSc. Keywords Systemic sclerosis . Therapeutic targets . Fibrosis . Metabolism . Immunity . Epigenetics
Introduction Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy, autoimmunity, inflammation, and fibrosis. SSc is an orphan disease with a prevalence of around 1/10,000 globally. However, SSc ranks top among all rheumatic diseases in terms of mortality [1, 2]. The highest mortality rate is associated with internal organ dysfunction. Uncovering the mechanism of fibrogenesis in SSc has been the main goal of generations of scientists. With our evolving Hanlin Yin and Rui Li contributed equally to this work. This article is part of the Topical Collection on Scleroderma * Liangjing Lu [email protected] * Qingran Yan [email protected] 1
Department of Rheumatology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, 145 Shandong Middle Road, Shanghai 200001, China
understanding of SSc pathogenesis, there arise many potential targets. In this review, we classify emerging targets into four broad categories: metabolic reprogramming intervention, immuneassociated targets, epigenetics, and developmental and death receptor signaling. For each category, we mainly discuss preclinical studies as well as clinical trials in the past 3 years.
Metabolic Reprogramming Intervention Activation and differentiation of immune cells occur si
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