Aldosterone promotes renal interstitial fibrosis via the AIF-1/AKT/mTOR signaling pathway
Aldosterone promotes renal interstitial fibrosis via the AIF-1/AKT/mTOR signaling pathway
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醛固酮通过 AIF-1/AKT/mTOR 信号通路促进肾间质纤维化
DOI：
10.3892/mmr.2019.10680
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发表时间：
2019-09
影响因子：
3.4
通讯作者：
Hao Lirong
中科院分区：
文献类型：
--
作者：
Yuan Xueying;Wang Xingzhi;Li Yushu;Li Xin;Zhang Shuyu;Hao Lirong
多项研究表明醛固酮在促进肾间质纤维化中发挥重要作用，但具体机制仍有待阐明。先前的一项研究表明，醛固酮的纤维化作用与RAW264.7巨噬细胞中同种异体移植物炎症因子1（AIF-1）的表达相关，并呈时间和浓度依赖性。然而，醛固酮促进肾间质纤维化的确切机制仍不清楚。在本研究中，醛固酮对肾脏炎症细胞浸润、胶原沉积以及AIF-1、磷脂酰肌醇3激酶（PI3K）、AKT丝氨酸/苏氨酸激酶（AKT）、哺乳动物雷帕霉素靶蛋白（mTOR）、氧化应激因子NADPH氧化酶2（NOX2）和核转录因子表达水平的影响 在正常大鼠、用醛固酮治疗的大鼠、用醛固酮和螺内酯治疗的大鼠以及仅用螺内酯治疗的大鼠（用作对照）中评估红细胞相关因子2（Nrf2）。还在单侧输尿管梗阻 (UUO) 大鼠的肾间质中研究了醛固酮对这些因素的影响。此外，AIF-1基因在巨噬细胞RAW264.7细胞中过表达并被敲低，随后研究了醛固酮对PI3K、AKT、mTOR、NOX2和Nrf2的影响。结果显示,醛固酮促进炎症细胞浸润、胶原沉积以及AIF-1、PI3K、AKT、mTOR和NOX2的表达,但抑制Nrf2的表达。在UUO组大鼠中，醛固酮还促进肾间质炎症细胞浸润、胶原沉积以及AIF-1、NOX2、PI3K、AKT和mTOR的表达，而与仅UUO组相比，醛固酮下调Nrf2的表达。在正常和 UUO 大鼠中，醛固酮的影响被螺内酯抵消。在体外，与未处理的细胞相比，醛固酮上调了RAW264.7细胞中AKT、mTOR、NOX2和Nrf2的表达水平。抑制 AIF-1 的表达会抑制醛固酮的作用，而 AIF-1 的过度表达会增强 RAW264.7 细胞中的这些作用。这些结果表明醛固酮通过上调AIF-1的表达促进肾间质纤维化，具体机制可能涉及AKT/mTOR和氧化应激信号传导。
A number of studies have shown that aldosterone serves an important role in promoting renal interstitial fibrosis, although the specific mechanism remains to be elucidated. A previous study revealed that the fibrotic effect of aldosterone was associated with the expression of allograft inflammatory factor 1 (AIF-1) in RAW264.7 macrophage cells, in a time- and concentration-dependent manner. However, the exact mechanism through which aldosterone promotes renal interstitial fibrosis remains unknown. In the present study, the effects of aldosterone on renal inflammatory cell infiltration, collagen deposition and the expression levels of AIF-1, phosphatidylinositol 3-kinase (PI3K), AKT serine/threonine kinase (AKT), mammalian target of rapamycin (mTOR), the oxidative stress factor NADPH oxidase 2 (NOX2) and nuclear transcription factor erythroid-related factor 2 (Nrf2) were assessed in normal rats, rats treated with aldosterone, rats treated with aldosterone and spironolactone and those treated with spironolactone only (used as the control). The effect of aldosterone on these factors was also investigated in the renal interstitium of unilateral ureteral obstruction (UUO) rats. Additionally, the AIF-1 gene was overexpressed and knocked down in macrophage RAW264.7 cells, and the effects of aldosterone on PI3K, AKT, mTOR, NOX2 and Nrf2 were subsequently investigated. The results showed that aldosterone promoted inflammatory cell infiltration, collagen deposition and the expression of AIF-1, PI3K, AKT, mTOR and NOX2, but inhibited the expression of Nrf2. In the UUO rats, aldosterone also promoted renal interstitial inflammatory cell infiltration, collagen deposition and the expression of AIF-1, NOX2, PI3K, AKT and mTOR, whereas the expression of Nrf2 was downregulated by aldosterone compared with that in the UUO-only group; the influence of aldosterone was counteracted by spironolactone in the normal and UUO rats. In vitro, aldosterone upregulated the expression levels of AKT, mTOR, NOX2 and Nrf2 in RAW264.7 cells compared with those in untreated cells. Suppressing the expression of AIF-1 inhibited the effects of aldosterone, whereas the overexpression of AIF-1 enhanced these effects in RAW264.7 cells. These findings indicated that aldosterone promoted renal interstitial fibrosis by upregulating the expression of AIF-1 and that the specific mechanism may involve AKT/mTOR and oxidative stress signaling.
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醛固酮刺激的巨噬细胞上调同种异体移植物炎症因子 1 的表达和分泌，促进肾成纤维细胞形成促纤维化表型
影响因子：
5.4
作者：
Li Y;Wang X;Zhang L;Yuan X;Hao J;Ni J;Hao L
通讯作者：
Hao L
DOI：
10.1186/2040-2384-1-2
发表时间：
2009-09-21
期刊：
Journal of angiogenesis research
影响因子：
--
作者：
Meadows KN;Iyer S;Stevens MV;Wang D;Shechter S;Perruzzi C;Camenisch TD;Benjamin LE
通讯作者：
Benjamin LE
影响因子：
3.7
作者：
Oh CJ;Kim JY;Choi YK;Kim HJ;Jeong JY;Bae KH;Park KG;Lee IK
通讯作者：
Lee IK
影响因子：
8.7
作者：
Autieri, MV;Carbone, CM
通讯作者：
Carbone, CM
影响因子：
6.1
作者：
Aminzadeh, Mohammad A.;Nicholas, Susanne B.;Vaziri, Nosratola D.
通讯作者：
Vaziri, Nosratola D.