Trans-repression of NFκB pathway mediated by PPARγ improves vascular endothelium insulin resistance.
Trans-repression of NFκB pathway mediated by PPARγ improves vascular endothelium insulin resistance.
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PPARgamma 介导的 NFkappaB 通路反式抑制可改善血管内皮胰岛素抵抗。
DOI：
10.1111/jcmm.13913
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发表时间：
2019-01
影响因子：
5.3
通讯作者：
Huang Q
中科院分区：
文献类型：
--
作者：
Kong Y;Gao Y;Lan D;Zhang Y;Zhan R;Liu M;Zhu Z;Zeng G;Huang Q
已有研究表明噻唑烷二酮类药物（TZDs）通过抑制PPARγ依赖的NFκB反式抑制机制改善高糖/高脂血症诱导的内皮细胞胰岛素抵抗（IR）。然而，PPARγ表达的变化是否影响内皮细胞IR及其机制尚不清楚。在本研究中，我们旨在解决这个问题。HG处理的人脐血管内皮细胞（HUVEC）通过过表达PPARγ（Ad-PPARγ）或含PPARγ-shRNA（Ad-PPARγ-shRNA）的腺病毒载体转染。同样地，通过静脉内施用Ad-PPAR γ或Ad-PPAR γ-shRNA感染高脂饮食（HFD）喂养的大鼠。检测一氧化氮（NO）、内皮素-1（ET-1）和细胞因子（TNFα、IL-6、sICAM-1和sVCAM-1）的水平以及过氧化物酶体增殖物激活受体γ（PPARγ）、内皮型一氧化氮合酶（eNOS）、AKT、p-AKT、IKK α/β和p-IKKα/β和IκBα的表达水平;评价PPARγ与NFκB-P65的相互作用以及血管功能。我们目前的研究结果表明，过表达PPARγ可显著增加NO、eNOS、p-AKT和IκBα的水平以及PPARγ与NFκB-P65的相互作用，并降低ET-1、p-IKK α/β、TNFα、IL-6、sICAM-1和sVCAM-1的水平。相反，过氧化物酶体增殖物激活受体γ的表达下降显示出相反的效果。结果表明，过表达的PPARγ通过NFκB反式抑制依赖的方式改善内皮细胞IR，而表达下调则通过NFκB反式抑制依赖的方式改善内皮细胞IR。结果表明，PPARγ是糖尿病血管并发症的潜在治疗靶点。
Previous study has shown that thiazolidinediones (TZDs) improved endothelium insulin resistance (IR) induced by high glucose concentration (HG)/hyperglycaemia through a PPARγ‐dependent‐NFκB trans‐repression mechanism. However, it is unclear, whether changes in PPARγ expression affect the endothelium IR and what the underlying mechanism is. In the present study, we aimed to address this issue. HG‐treated human umbilical vascular endothelial cells (HUVEC) were transfected by either PPARγ‐overexpressing (Ad‐PPARγ) or PPARγ‐shRNA‐containing (Ad‐PPARγ‐shRNA) adenoviral vectors. Likewise, the rats fed by high‐fat diet (HFD) were infected by intravenous administration of Ad‐PPARγ or Ad‐PPARγ‐shRNA. The levels of nitric oxide (NO), endothelin‐1 (ET‐1) and cytokines (TNFα, IL‐6, sICAM‐1 and sVCAM‐1) and the expression levels of PPARγ, eNOS, AKT, p‐AKT, IKKα/β and p‐IKKα/β and IκBα were examined; and the interaction between PPARγ and NFκB‐P65 as well as vascular function were evaluated. Our present results showed that overexpression of PPARγ notably increased the levels of NO, eNOS, p‐AKT and IκBα as well as the interaction of PPARγ and NFκB‐P65, and decreased the levels of ET‐1, p‐IKKα/β, TNFα, IL‐6, sICAM‐1 and sVCAM‐1. In contrast, down‐expression of PPARγ displayed the opposite effects. The results demonstrate that the overexpression of PPARγ improves while the down‐expression worsens the endothelium IR via a PPARγ‐mediated NFκB trans‐repression dependent manner. The findings suggest PPARγ is a potential therapeutic target for diabetic vascular complications.
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影响因子：
64.8
作者：
Banks, Alexander S.;McAllister, Fiona E.;Camporez, Joao Paulo G.;Zushin, Peter-James H.;Jurczak, Michael J.;Laznik-Bogoslavski, Dina;Shulman, Gerald I.;Gygi, Steven P.;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1016/j.bbadis.2013.05.017
发表时间：
2014-03
影响因子：
6.2
作者：
Lee, Byung-Cheol;Lee, Jongsoon
通讯作者：
Lee, Jongsoon
影响因子：
2.9
作者：
Alemán-González-Duhart D;Tamay-Cach F;Álvarez-Almazán S;Mendieta-Wejebe JE
通讯作者：
Mendieta-Wejebe JE
影响因子：
2.7
作者：
Kearney, Mark T.;Duncan, Edward R.;Wheatcroft, Stephen B.
通讯作者：
Wheatcroft, Stephen B.
影响因子：
9.3
作者：
Liepinsh, Edgars;Makrecka-Kuka, Marina;Dambrova, Maija
通讯作者：
Dambrova, Maija