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논문분류	춘계학술대회 초록집
제목	Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease
저자	Hong Sang Choi, Ha Yeon Kim, Chang Seong Kim, Seong Kwon Ma, Soo Wan Kim, Eun Hui Bae
출판정보	2018; 2018(1):
키워드	CG200745 \| HDAC inhibitor \| UUO \| fibrosis \| inflammation
초록	Objectives: Tubulointerstitial fibrosis is a common feature of kidney disease. Histone deacetylase (HDAC) inhibitors have been reported to attenuate progression of renal fibrosis. In this study, we investigated the effect of CG200745, a novel HDAC inhibitor, on development of renal fibrosis in a mouse model of unilateral ureteral obstruction. Methods: To examine the effects of CG200745 in unilateral ureteral obstruction (UUO), C57BL6 male mice were divided into three groups: control, UUO, and CG200745(30mg/kg/day) treated UUO mice. CG 200745 was administered through drinking water for 1 week. We also treated human proximal tubular epithelial (HK-2) cells with CG200745(10uM) with or without TGF-β1 (2 ng/mL). Results: At seventh day after UUO, kidney developed marked fibrosis as indicated by deposition of collagen in Masson’s trichrome stain and increased expression of α-smooth muscle actin (SMA) and fibronectin. Treatment with CG200745 attenuated these fibrotic responses. CG200745 treatment also suppressed UUO induced production of transforming growth factor-beta1 (TGF-β) and phosphorylation of Smad-2/3. Treatment of CG200745 attenuated UUO-induced inflammation as indicated by decreased expression of heme oxygenase 1, F4/80, and mRNA expression of tumor necrosis factor alpha(TNF-α), monocyte chemotactic protein 1(MCP-1), intercellular adhesion molecule 1(ICAM-1) and vascular cell adhesion molecule 1(VCAM-1). Further, CG200745 attenuated phosphorylation of p38 mitogen-activated protein kinase (p38-MAPK) in UUO kidneys. In HK-2 cells, TGF-β induced the expression of α-SMA and fibronectin, which were attenuated by CG200745 cotreatment. Conclusions: These results demonstrate that CG200745, a novel HDAC inhibitor, have renoprotective effect by suppressing renal fibrosis and inflammation in UUO mouse model.
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