Epigenetics, the holy grail in the pathogenesis of systemic sclerosis

N Altorok, N Almeshal, Y Wang, B Kahaleh - Rheumatology, 2015 - academic.oup.com
N Altorok, N Almeshal, Y Wang, B Kahaleh
Rheumatology, 2015academic.oup.com
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 …
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.
Oxford University Press