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논문분류	춘계학술대회 초록집
제목	Effects of Resveratrol on Renin-Angiotensin System in the Aging Kidney
저자	In-Ae Jang* 1, Eun Nim Kim1, Ji Hee Lim1, Min Young Kim1, Tae Hyun Ban1, Hye Eun Yoon1, Byung Ha Chung1,
출판정보	2016; 2016(1):
키워드	Aging kidney, Mas receptor, Renin-angiotensin system, Resveratrol
초록	Background: The renin-angiotensin system, especially angiotensin II (ANGII) / angiotensin II type 1 receptors (AT1R) axis plays an important role in the aging process of kidney through increased tissue reactive oxygen species production and progressively increased oxidative stress, while the angiotensin II type 2 receptors (AT2R) and angiotensin 1–7/Mas receptor (MasR) axis, which has counteracting effects on ANGII, is protective for end-organ damage. In the present study, we aimed to evaluate the effect of resveratrol, a naturally found polyphenol with variety of bioactivities, including antioxidant, anti-inflammatory, anti-senescent activity, in modulation of reninangiotensin system in aging kidney of mice and to identify the putative underlying signaling pathways. Methods: 18-month-old male C57BL/6 mice were divided into two groups and received either normal mice chow or underwent resveratrol treatment for 6 months. Intrarenal expression of ANGII, AT1R, AT2R, angiotensin converting enzyme (ACE) and ACE2, as well as pro- and antioxidant enzymes (endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosin, superoxide dismutase 1 and 2 (SOD1 and SOD2), fibronectin, collagen IV and transforming growth factor-β) were measured, and mice kidney was isolated for histological assays. Results: Resveratrol-treated group showed significant improvement in renal function; serum creatinine decreased (0.25 ± 0.05 mg/dL vs. 0.67 ± 0.34 mg/dL; p <0.03 vs. control group), creatinine clearance increased (0.28 ± 0.07 ml/min vs. 0.10 ± 0.04 ml/min; p <0.001 vs. control group) and albuminuria decreased (29.47 ± 14.32 μg/24hr vs. 67.69 ± 22.79 μg/24hr; p <0.03 vs. control group) compared with control group. There were decreases in mesangial volume (42.87 ± 1.25% vs. 56.1 ± 2.06%; p <0.001 vs. control group) and tubulointerstitial fibrosis (4.84 ± 5.58% vs. 10.17 ± 3.36%; p <0.05 vs. control group) in resveratrol-treated oldmice. The expressions of ANGII, ACE and AT1R significantly decreased in resveratrol-treated group, whereas those of ACE2, AT2R and MasR increased. Resveratrol increased the expression of phosphorylated eNOS significantly and SOD1 and SOD2 were also increased but there was no statistical meaning. The expressions of fibronectin and collagen IV significantly decreased and while the expression of Nox4 significantly decreased, that of Nox2 did not change. Immunohistochemistry revealed that the 8-OHdG-positive area and the 3-nitrotyrosin-positive area decreased in resveratrol-treated group. Conclusion: Resveratrol exerts renoprotective effects on aging kidney, associated with reduction of oxidative stress, inflammation and fibrosis through AT2R and MasR activation. Thus, this study provides important insight into the molecular pathways that may contribute to the proposed beneficial effects of resveratrol on the renin-angiotensin system in aging kidney. Figures: Keywords:
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