Histone Acetylation and Its Modifiers in the Pathogenesis of Diabetic Nephropathy

Table 1

Reported histone lysine and nonhistone acetylation in DN.

Ac proteins	Acetylation site	Target genes	Target renal loci	Effects in DN	References
Histone lysine	H3K9	MCP-1, ICAM-1, andVCAM-1; TXNIP	db/db mice kidney; Akita mice renal cortex, MCs	Advanced diabetic glomerulosclerosis; inflammation	[32–34]
	H3K9/14	TNF-α, COX-2; MCP-1, IL-6; PAI-1, p21; RAGE; CTGF, FN	Human blood monocytes; rat VSMCs; MMCs, db/db mice glomeruli; RMCs; STZ-induced mice	Inflammation; increased miR-192 expression; hypertrophy, fibrosis	[30, 31, 35, 36, 38, 39]
	H3K18	MCP-1, ICAM-1, and VCAM-1	Akita mice renal cortex, MCs	Advanced diabetic glomerulosclerosis; inflammation	[33]
	H3K23		db/db mice kidney	Advanced diabetic glomerulosclerosis	[32, 33]
	H3K27		MMCs, db/db mice glomeruli	Increased miR-192 expression	[35]
	H4	GRP78, CHOP	STZ-induced rat kidney	Cell apoptosis, proteinuria, and increase of Scr	[44]
	H4K5/8/12	TNF-α, COX-2	Human blood monocytes	Inflammation	[30]
Nonhistone proteins	Ets-1		MMCs, db/db mice glomeruli	Increased miR-192 expression	[35]
	Foxo4	Bcl2111	Podocyte	Promoting apoptosis	[45]
	NF-κB	TGF-β1, FN, and type IV collagen	RMCs, diabetic rats	UAE increase, matrix expansion, and ECM deposition	[46]
	NF-κB p65	MCP-1, PAI-1, and TGF-β1	Mice and human diabetic kidneys, human podocytes; RMCs;	Kidney injury; inflammation;	[47, 48]
	STAT3		mice and human diabetic kidneys; human podocytes	Kidney injury	[47]
	Smad3	SREBP-1; type IV collagen	MMCs; iHMCs	Inducing glomerulosclerosis, increased albuminuria	[49, 50]
	Nephrin	WT-1, TGF-β1, and FN	STZ-induced FVB mice, podocyte	Ameliorate HG-induced podocyte dysfunction	[51]