Epigenetic Modifications in the Pathogenesis of Systemic Sclerosis

Figures & data

Figure 1 Epigenetic regulation in the pathogenesis of SSc. The pathogenesis of SSc is characterized by three processes: immune disorders, vascular damage and fibrosis. A large number of studies have shown that epigenetics plays a vital role in the pathogenesis of SSc. IFI44L, RSAD2, IFIT1, IRF7 and other IFN related genes are highly expressed in the blood due to hypomethylation; anti-Ro and anti-topoisomerase positive and ACA negative are related with IFN highly expression; the up-regulation of miR-618 and NRIR are also associated with IFN production. These controls have led to the high IFN expression pattern of SSc. The down-regulation of PARP-1 and miR-29a, and the up-regulation of EZH2 and miR-21 participate in the TGF-β pathway and activate fibroblasts into myofibroblasts. In addition, the decrease of BMPRII and NOS3, the increase of EZH2, HDAC5, and miR-483-5p are involved in vascular injury.

Table 1 Epigenetic Regulation in the Pathogenesis of SSc

Epigenetics	Type	Change	Expression	Cell/Tissue	Reference
DNA methylation	IFI44L	Hypomethylation	Increased	Blood	[^Citation24^–^Citation26]
	RSAD2	Hypomethylation	Increased	Blood/CD4+T	[^Citation24^–^Citation26]
	TYROBP	Hypomethylation	Increased	Blood	[^Citation26]
	FOXP3	Hypermethylation	Decreased	CD4+T	[^Citation33]
	CD40L	Hypomethylation	Increased	CD4+T	[^Citation35]
	PAX9	Hypomethylation		Fibroblast	[^Citation37]
	TNXB	Hypomethylation		Fibroblast	[^Citation37]
	TET1	Hypomethylation	Increased	Fibroblast	[^Citation38]
	PARP-1	Hypermethylation	Decreased	Fibroblast	[^Citation39]
	DLX5	Hypomethylation	Increased	Fibroblast	[^Citation40]
	TMEM140	Hypomethylation	Increased	Fibroblast	[^Citation40]
	BMPRII	Hypermethylation	Decreased	Endothelial	[^Citation49]
	NOS3	Hypermethylation	Decreased	Endothelial	[^Citation50]
Histone modification	Global histone H4	Hyperacetylation		B cell	[^Citation53]
	FLI1	Deacetylation	Decreased	Fibroblast	[^Citation41]
	H3K27me3		Increased	Fibroblast/endothelial	[^Citation57,Citation58]
	HDAC5		Increased	Endothelial	[^Citation60]
Non-coding RNA	miR-483-5p		Increased	Serum/fibroblast/endothelial	[^Citation63]
	miR-5196		Increased	Serum/monocyte	[^Citation65]
	miR-618		Increased	Peripheral blood PDC	[^Citation66]
	miR-200C		Increased	PBMC	[^Citation68]
	miR-21		Increased	Fibroblast	[^Citation72]
	miR-29a		Decreased	Fibroblast	[^Citation72]
	NRIR		Increased	Monocyte	[^Citation89]
	SPRY4-IT1		Increased	Plasma	[^Citation90]
	HOTTIP		Increased	Plasma	[^Citation90]
	ANCR		Decreased	Plasma	[^Citation90]
	TINCR		Increased	Plasma	[^Citation90]
	OTUD6B-AS1		Decreased	Fibroblast, human pulmonary artery smooth muscle cells	[^Citation91]
	H19X		Increased	Fibroblast	[^Citation92]
	TSIX		Increased	Fibroblast, serum	[^Citation94]
	HOTAIR		Increased	Fibroblast	[^Citation59]
	ncRNA00201		Decreased	PBMC	[^Citation96]
	PSMB8-AS1		Increased	PBMC	[^Citation97]
	MGC12916		Decreased	Fibroblast	[^Citation40]

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