Unfolding the pathogenesis of systemic sclerosis through epigenomics

Abstract

As a group of autoimmune diseases, systemic sclerosis (scleroderma, SSc) is characterized by immune dysregulation, micro-vessels dominant obliteration, and the final fibrosis of the skin and or internal organs. Although the precise mechanisms are still unknown, increasing data shows that epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA (miRNA), are strictly related to the pathogenesis of scleroderma. Epigenetic mechanisms, which can link genetics and environmental stress, represents a promising field in systemic sclerosis investigation. The objective of this review is, to sum up the current information about epigenetic alteration.

Leeches alleviates diabetic macroangiopathy by increasing nitric oxide production in rat aorta and restoring endothelium-dependent vasodilatation

“…Macroangiopathy is one of the most common complications in diabetic patients, and currently the major cause of morbidity and mortality in patients with type 1 and type 2 diabetes. Compared to non-diabetic individuals, diabetic patients are more prone to atherosclerosis that can be attributed to epigenetic factors [29], which also develops rapidly to coronary heart disease, cerebrovascular accidents and gangrene of lower limbs. According to previous reports, 20% of patients with peripheral vascular diseases were found to have diabetes.…”

FBXL6 is dysregulated in keloids and promotes keloid fibroblast growth by inducing c‐Myc expression

“…6 Keloid fibroblasts are implicated as principal mediators to remodel the scar tissue, which possesses the overproliferation and apoptosis resistance characteristics to produce collagen fibres and other extracellular matrices. [7][8][9] C-MYC-mediated fibroblasts proliferation and collagen deposition are vital in keloids. 10,11 On the other hand, the ubiquitin-proteasome system is also reported to be involved in keloid fibroblasts proliferation, differentiation and collagen secretion in keloids.…”

“…Keloid fibroblasts are implicated as principal mediators to remodel the scar tissue, which possesses the over‐proliferation and apoptosis resistance characteristics to produce collagen fibres and other extracellular matrices 7‐9 . C‐MYC‐mediated fibroblasts proliferation and collagen deposition are vital in keloids 10,11 .…”

The deubiquitinating enzyme USP37 promotes keloid fibroblasts proliferation and collagen production by regulating the c‐Myc expression

“…Keloid is a group of pathological fibroproliferative skin disorders with unremitting extracellular matrix (ECM) accumulation, remodelling, and stiffness 1,2 . Although the pathogenesis of keloid is complex, strong genetic predisposition, growth factors' profile alteration, collagen turnover, and higher stretching tension contribute to keloid formation and development 3‐5 . Surgery, steroid, and radiation treatment are recommended in clinics, while the high recurrence and accompanying psychological distress still pose a challenge for affected patients 6,7 …”

“…1,2 Although the pathogenesis of keloid is complex, strong genetic predisposition, growth factors' profile alteration, collagen turnover, and higher stretching tension contribute to keloid formation and development. [3][4][5] Surgery, steroid, and radiation treatment are recommended in clinics, while the high recurrence and accompanying psychological distress still pose a challenge for affected patients. 6,7 Myofibroblasts derived from resident skin fibroblasts are the principal mediators responsible for ECM accumulation, demonstrating apoptosis resistance and hyperproliferation characteristics.…”