title: Epigenetics, the holy grail in the pathogenesis of systemic sclerosis.
abstract: The objective of this review is to present evidence that supports the central role of epigenetic regulation in the pathogenesis of SSc. SSc is a complex autoimmune disease characterized by immune activation, fibrosis of the skin and internal organs and obliterative vasculopathy affecting predominantly the microvessels. Remarkable progress has been made in the past few years emphasizing the importance of epigenetic modifications in the pathogenesis of many disorders, including SSc. Current evidence demonstrates alterations in DNA methylation, histone code modifications and changes in microRNA (miRNA) expression levels in SSc cells. Recent reports have described the differential expression of numerous regulatory miRNAs in SSc, mainly in SSc fibroblasts, a number of which are important in TGF-β pathways and downstream signalling cascades. While studies to date have revealed the significant role of epigenetic modifications in the pathogenesis of SSc, the causal nature of epigenetic alterations in SSc pathogenesis remains elusive. Additional longitudinal and comprehensive epigenetic studies designed to evaluate the effect of environmental epigenetic factors on disease pathogenesis are needed.
authors.affiliation: Division of Rheumatology and Immunology and Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: Nezam
authors.initials: N
authors.lastname: Altorok
authors.affiliation: Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: Nawaf
authors.initials: N
authors.lastname: Almeshal
authors.affiliation: Division of Rheumatology and Immunology and.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Rheumatology and Immunology and Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA bashar.kahaleh@utoledo.edu.
authors.forename: Bashar
authors.initials: B
authors.lastname: Kahaleh
mesh_terms: D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology; D057890:Epigenomics; D042421:Histone Code / Q000235:genetics / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology; D012595:Scleroderma, Systemic / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D035683:MicroRNAs
keywords: DNA methylation; endothelial cells; epigenetic; fibroblasts; fibrosis; friend leukaemia integration 1 transcription factor; histone modifications; microRNA; nitric oxide synthase; scleroderma