Epigenetics of Systemic Sclerosis

  • Nezam Altorok
  • Vivek Nagaraja
  • Bashar KahalehEmail author
Reference work entry


Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by vascular dysfunction, activation of the immune system, and tissue fibrosis. SSc is associated with high mortality and morbidity. The precise etiology of SSc is undetermined, but there is evidence suggestive of a link between environmental factors and SSc pathogenesis. In this chapter, we will define and discuss the various clinical manifestations of SSc, and then we will review the evidence of environmental factor role in SSc. Next, we will evaluate the evidence for epigenetic regulation in SSc and the potential role of epigenetic aberrancies in SSc pathogenesis.


Scleroderma Systemic sclerosis Epigenetics DNA methylation Histone modification MicroRNA Fibroblasts Fibrosis Microvascular endothelial cells Environment Silica 

List of Abbreviations

ACE inhibitors

Angiotensin converting enzyme inhibitors


Actin, alpha 2, smooth muscle, aorta gene


American College of Rheumatology


Bone morphogenetic protein type II receptor


Diffuse cutaneous systemic sclerosis


DNA (cytosine-5-)-methyltransferase 1


Extracellular matrix


Eosinophilia-myalgia syndrome




Friend leukemia virus integration gene




Trimethylation of histone H3 on lysine 27


Limited cutaneous systemic sclerosis


Localized scleroderma


Methyl-CpG-binding domain protein1


Metacarpal phalangeal joints


Methyl-CpG-binding protein 2


Matrix metalloproteinase 1


Microvascular endothelial cells


Nephrogenic fibrosing dermopathy


Nitric oxide synthase


Nephrogenic systemic fibrosis


Pulmonary arterial hypertension




Polyvinyl chloride


Raynaud’s phenomenon


Intracellular proteins that transduce extracellular signals from TGF-β ligands


Scleroderma renal crisis


Systemic sclerosis






Transforming growth factor-β


Toxic oil syndrome


Vinyl chloride


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Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal MedicineUniversity of Toledo Medical CenterToledoUSA

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