Ocular expression of cyclin-dependent kinase 5 in patients with proliferative diabetic retinopathy.
Ocular expression of cyclin-dependent kinase 5 in patients with proliferative diabetic retinopathy.
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DOI：
10.1111/jdi.13702
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发表时间：
2022-04
影响因子：
3.2
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中科院分区：
文献类型：
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抑制细胞周期蛋白依赖性激酶5（Cdk 5）介导的过氧化物酶体增殖物激活受体γ（PPARγ）磷酸化是抗糖尿病药物的主要作用机制之一。在这项研究中，我们分析了Cdk5在增殖性糖尿病视网膜病变（PDR）患者中的眼部表达和活化。采用酶联免疫吸附法（ELISA）检测24例PDR和63例对照眼玻璃体中PPARγ、Cdk5及其活化亚基（p35）的浓度。此外，通过定量真实的时间聚合酶链反应和免疫组织化学分析，测量了7只PDR眼的增生性新生血管膜和5只对照眼的非新生血管性视网膜前膜中PPARγ、Cdk 5和p35的信使核糖核酸和蛋白表达水平。PDR组玻璃体中的PPARγ、Cdk5和p35浓度明显高于对照组。PDR组中Cdk 5与PPARγ、p35的表达呈正相关。PDR组增生血管膜中PPARγ、Cdk5和p35的mRNA表达水平明显高于对照组。免疫组化显示PDR组增生新生血管膜中的PPARγ、Cdk 5和p35蛋白表达水平较对照组升高。Cdk5活化通过PPARγ表达参与PDR的发病过程，抑制Cdk5介导的PPARγ磷酸化可能成为治疗PDR的新靶点。增殖性糖尿病视网膜病变眼的细胞周期蛋白依赖性激酶5及其激活子亚单位（p35）浓度显著高于对照组，并且在增殖性糖尿病视网膜病变眼中发现细胞周期蛋白依赖性激酶5和过氧化物酶体增殖物激活受体γ的表达之间存在显著相关性。我们的数据表明，细胞周期蛋白依赖性激酶5可能通过过氧化物酶体增殖物激活受体γ参与增殖性糖尿病视网膜病变的发病机制。
Inhibition of peroxisome proliferator‐activated receptor gamma (PPARγ) phosphorylation mediated by cyclin‐dependent kinase 5 (Cdk5) is one of the main mechanisms of action of antidiabetic drugs. In this study, we analyzed the ocular expression and activation of Cdk5 in patients with proliferative diabetic retinopathy (PDR). The concentrations of PPARγ, Cdk5 and its activating subunit (p35) were determined in the vitreous body of 24 PDR and 63 control eyes by enzyme‐linked immunosorbent assay. In addition, the messenger ribonucleic acid and protein expression levels of PPARγ, Cdk5 and p35 were measured in proliferative neovascular membranes from seven PDR eyes and non‐neovascular epiretinal membranes from five control eyes by quantitative real‐time polymerase chain reaction and immunohistochemical analysis. PPARγ, Cdk5 and p35 concentrations in the vitreous body were significantly higher in the PDR group compared with the control group. There was also a positive significant correlation of Cdk5 with PPARγ and p35 in the PDR group. Furthermore, the messenger ribonucleic acid expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes were significantly higher in the PDR group compared with the control group. Immunostaining showed increased protein expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes in the PDR group compared with the control group. Cdk5 activation is involved in PDR pathogenesis through PPARγ expression, and inhibition of Cdk5‐mediated PPARγ phosphorylation might be a new therapeutic target for treatment of PDR. The concentrations of cyclin‐dependent kinase 5 and its activator subunit (p35) were significantly higher in eyes with proliferative diabetic retinopathy than in controls, and a significant correlation was found between the expression of cyclin‐dependent kinase 5 and peroxisome proliferator‐activated receptor gamma in proliferative diabetic retinopathy eyes. Our data suggested that cyclin‐dependent kinase 5 might be involved in the pathogenesis of proliferative diabetic retinopathy through peroxisome proliferator‐activated receptor gamma.
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影响因子：
--
作者：
Herzog J;Ehrlich SM;Pfitzer L;Liebl J;Fröhlich T;Arnold GJ;Mikulits W;Haider C;Vollmar AM;Zahler S
通讯作者：
Zahler S
影响因子：
64.8
作者：
通讯作者：
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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.
影响因子：
4.1
作者：
Limb, GA;Chignell, AH;Dumonde, DC
通讯作者：
Dumonde, DC
影响因子：
3.9
作者：
Demircan, N.;Safran, B. G.;Sizmaz, S.
通讯作者：
Sizmaz, S.