Understanding Fibrosis in Systemic Sclerosis: Novel and Emerging Treatment Approaches.

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. New targets involved in metabolic reprogramming, immunity, epigenetics together with developmental and apoptotic pathways open new avenues for therapeutic modulation in SSc.