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논문분류	춘계학술대회 초록집
제목	Histone deacetylase inhibitor, CG200745, attenuates renal fibrosis in DOCA-salt Hypertensive Rats
저자	Eun Hui Bae, Hong sang Choi, Ha Yeon Kim, Chang Seong Kim, Seong Kwon Ma, Young Jin Kim, Jeong Whan Woon
출판정보	2018; 2018(1):
키워드	DOCA-salt \| CG200745 \| hypertension \| ; glomerulosclerosis \| fibrosis
초록	Objectives: CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancer. HDAC inhibitors also have known as blocking cardiac hypertrophy and fibrosis. This study investigated the renoprotective effects of CG200745 and their molecular mechanisms in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats. Methods: DOCA strips (200 mg/kg) were implanted in rats 1 week after unilateral nephrectomy. Two weeks after DOCA implantation, DOCA-salt rats were randomly divided to receive CG200745 (5 mg·kg−1day−1) or not for another 2 weeks. Systolic blood pressure (SBP) was measured by the tail cuff method, and the urinary albumin-to-creatinine ratio (ACR) was calculated. The extent of glomerulosclerosis and tubulointerstitial fibrosis was determined by Masson’s trichrome stain. Renal expression of alpha smooth muscle (αSMA), transforming growth factor-β1 (TGF-β1), Bax, and Bcl-2 were determined by semiquantitative immunoblotting, polymerase chain reaction (PCR), and immunohistochemistry. TUNEL staining was used for detecting apoptotic cells. Results: The increased SBP in DSH rats was attenuated by CG200745 treatment. The decreased creatinine clearance and increased ACR in DSH rats, compared with control animals, were attenuated by CG200745 treatment. Further, CG200745 treatment attenuated glomerulosclerosis and tubulointerstitial fibrosis in DSH rats and counteracted the increased expression of αSMA, TGF-β1, and Bax and the decreased expression of Bcl-2 in the kidneys of these rats. The increase in the number of apoptotic cells in DSH rats was attenuated by CG200745 treatment. Conclusions: CG200745 effectively prevented the progression of renal injury in DSH rats via its anti-inflammatory, antifibrotic, and antiapoptotic effects.
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