SIRT3-KLF15 signaling ameliorates kidney injury induced by hypertension.
SIRT3-KLF15 signaling ameliorates kidney injury induced by hypertension.
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DOI：
10.18632/oncotarget.17165
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发表时间：
2017-06-13
期刊：
影响因子：
--
通讯作者：
Bu P
中科院分区：
文献类型：
--
作者：
Li N;Zhang J;Yan X;Zhang C;Liu H;Shan X;Li J;Yang Y;Huang C;Zhang P;Zhang Y;Bu P
肾纤维化参与了高血压肾损伤的发展过程。SIRT3是NAD+依赖的脱乙酰酶家族的一员，其在高血压肾病中的作用尚不清楚。在本研究中，我们发现血管紧张素II(AngII)在体内和体外处理后，SIRT3均降低。此外，SIRT3基因敲除小鼠通过慢性血管紧张素Ⅱ输注(每分钟2000 ng/kg，持续42天)加重了高血压引起的肾功能障碍和肾脏纤维化。相反，与野生型小鼠相比，SIRT3过表达小鼠减轻了血管紧张素转换酶I诱导的肾脏损伤。值得注意的是，SIRT3和KLF15(一种富含肾脏的核转录因子)的共同定位导致SIRT3直接使KLF15去乙酰化，随后在培养的MPC-5足细胞中纤维连接蛋白和IV型胶原的表达减少。厚朴中的主要活性成分和厚朴酚(HKL)通过激活SIRT3-KLF15信号通路抑制Angii诱导的肾纤维化。综上所述，我们的研究结果表明，一个新的SIRT3-KLF15信号可能预防高血压引起的肾脏损伤，HKL可能作为SIRT3-KLF15信号激活剂来保护高血压肾病。
Renal fibrosis participates in the progression of hypertension-induced kidney injury. The effect of SIRT3, a member of the NAD+-dependent deacetylase family, in hypertensive nephropathy remains unclear. In this study, we found that SIRT3 was reduced after angiotensin II (AngII) treatment both in vivo and in vitro. Furthermore, SIRT3-knockout mice aggravated hypertension-induced renal dysfunction and renal fibrosis via chronic AngII infusion (2000 ng/kg per minute for 42 days). On the contrary, SIRT3-overexpression mice attenuated AngII-induced kidney injury compared with wild-type mice. Remarkably, a co-localization of SIRT3 and KLF15, a kidney-enriched nuclear transcription factor, led to SIRT3 directly deacetylating KLF15, followed by decreased expression of fibronectin and collagen type IV in cultured MPC-5 podocytes. In addition, honokiol (HKL), a major bioactive compound isolated from Magnolia officinalis (Houpo), suppressed AngII-induced renal fibrosis through activating SIRT3-KLF15 signaling. Taken together, our findings implicate that a novel SIRT3-KLF15 signaling may prevent kidney injury from hypertension and HKL can act as a SIRT3-KLF15 signaling activator to protect against hypertensive nephropathy.
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DOI：
10.1042/cs20120190
发表时间：
2013-02
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Kitada M;Kume S;Takeda-Watanabe A;Kanasaki K;Koya D
通讯作者：
Koya D
影响因子：
19.6
作者：
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DOI：
10.3390/v7092852
发表时间：
2015-09-10
期刊：
Viruses
影响因子：
--
作者：
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通讯作者：
Huang KJ
影响因子：
12.8
作者：
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Kim CW
影响因子：
8.3
作者：
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通讯作者：
Carretero, Oscar A.