Table 1.

Genes that can be regulated by epigenetic changes in the development of organ fibrosis.

	Organs involved in fibrosis					Epigenetic mechanism
Gene	Lungs	Skin	Liver	Kidney	Intestine	Methylation	Histone modification	miRNA	References
Smad3	↑	↑	↓	↑	↑	N/A	HDAC1	miR-21, miR-154, miR-29	64, 69, 70, 75–77
Smad7	↓	↓	↓	↓	↓	DNMT1	N/A	miR-21, miR-17-5 p	44, 78, 79
SOCS3	↓	N/A	↓	↓	↓	DNMT1	N/A	miR-19 b	11, 12, 40
MMP	↑	↑	↑	↑	↑	Promoter	HDAC	miR-17, miR-18 a, b & miR-19 a, b,	50, 51, 95
α-SMA	↑	↑	↑	↑	↑	CpG, DNMT1, DNMT3b	H3K4me1	N/A	39, 41
COL	↑	↑	↑	↑	↑	DNMT1, DNMT3b	H4 acetylation, Fli-1 acetylation, H3K4me1	miR-18 a, b & miR-19 a, b, miR-29	38, 41, 54, 66, 67, 71, 72
VMP1	N/A	N/A	N/A	N/A	↑	N/A	N/A	miR-21	42
TGF-β1	↑	↑	↑	↑	↑	Smad7 methylation, Smad4 hypermethylation	H3K4me3↑, H2A.Z↑, ↓H3K9me2 and H3K9me3 on the promoters of ECM genes	miR-21, miR-17 & miR-19 a, b	43, 44
COX2	↓	↑	↑/↓	↑	↓	Promoter hypermethylation or hypomethylation	↓histone H3 and H4 acetylation, ↑ in H3K9me3, H3K27me3, and DNA methylation	Reported mostly in cancer research, miR-101, miR-26 b, miR-146 a, miR-16 and miR-122	52, 38, 80–88
CXCL10	↓	↑	↑	↓	↑	N/A	H3	unknown	53, 91–94
TIMP1	↑/↓	↓	↑	↑	↑	DNMT1	H3K4me1	miR-17, miR-29, miR-1293	54, 95, 96
Fli-1	↓	N/A	N/A	N/A	N/A	Promoter hypermethylation	P300-induced acetylation	N/A	33, 89, 90
Spry-1	↓	↓	↓	↓	↓	Promoter hypermethylation	HDAC↑ Spry-1 gene expression	miR-29, miR-21	66, 100
PTEN	↓	↓	↓	↓	↓	DNMT1-induced hypermethylation	Its interaction with histone H1 to keep chromatin condensation	miR-21	43, 97–99
PPAR-α	↓	↓	↓	↓	↓	Promoter hypermethylation	N/A	miR-21, miR-10 b, miR-33 a	62–64, 101–105
STAT3	↑	↑	↑	↑	↑	DNMT1,	HDACs, SET1, LSD1, EZH2	miR-21, miR-17, miR-29, miR-98	43, 66–70, 106–109
Thy-1	↓	↑	↑	↓/↑	↑	DNMT1, Hypermethylation	H3, HDAC inhibitor	N/A	52, 53, 110–113
IL-27	↓/↑	↑	↓	↓/↑	↓	N/A	N/A	N/A	29, 114–117
NOD2	↓/↑	N/A	↑	N/A	↓	DNA methylation	H3K4Me2 and H4Ac, H3K27Me3 histone modifications	miR-29, miR-192	29, 124–130
TNF-α	↑	↑	↑	↑	↑	DNA demethylation	Histone acetylation, H3K9 and H3K4 methylation	miR-23 a, miR-155, miR-346	29, 118–123
SMT1	↑	N/A	↑	↑	↓	DNA methylation	N/A	N/A	29, 131
IL-19	↑	↑	N/A	↑	↓	N/A	N/A	N/A	29

↑: upregulation; ↓: downregulation; ↓/↑: conflicting evidence; N/A: study not done.