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糖尿病Wistar大鼠心血管水平上孤儿GPR135的功能及表达改变

Altered function and expression of the orphan GPR135 at the cardiovascular level in diabetic Wistar rats.

作者信息

Ruiz-Hernández Armando, Romero-Nava Rodrigo, Huang Fengyang, Hong Enrique, Villafaña Santiago

机构信息

a Laboratorio de Señalización Intracelular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional , Ciudad de México , México.

b Laboratorio de Investigación en Farmacología, Hospital Infantil de México "Federico Gómez" , Ciudad de México , México.

出版信息

J Recept Signal Transduct Res. 2018 Oct-Dec;38(5-6):484-491. doi: 10.1080/10799893.2019.1597116.

Abstract

Cardiovascular complications are the main cause of mortality in patients with diabetes, these have been associated with changes in function and expression of receptors coupled to G proteins (GPCR), which include orphan receptors which some of them tend to modify in diabetes, although others are not known, such as GPR135. For this reason, the objective of this work was to study the expression of the orphan receptor GPR135 in brain, heart, kidney, aorta, lung, spleen and liver of diabetic rats, as well as its function by the administration of siRNA (small interfering RNA) and curves to isoproterenol. Our results showed that GPR135 is expressed in all tissues analyzed and its expression is modified due to diabetes, we also observed that the responses to isoproterenol increase in diabetic rats administered with siRNA. Therefore, we conclude that the orphan receptor GPR135 is expressed in different tissues and its expression tends to be modified due to diabetes, besides that it is functional and that it seems to be coupled to Gi/o protein which has negative chronotropic and inotropic effects, therefore, we do not rule out that it participates in the cardiovascular complications associated with diabetes.

摘要

心血管并发症是糖尿病患者死亡的主要原因,这些并发症与G蛋白偶联受体(GPCR)的功能和表达变化有关,其中包括一些在糖尿病中容易发生改变的孤儿受体,尽管其他一些受体尚不清楚,如GPR135。因此,本研究的目的是研究孤儿受体GPR135在糖尿病大鼠脑、心脏、肾脏、主动脉、肺、脾脏和肝脏中的表达,以及通过给予小干扰RNA(siRNA)和异丙肾上腺素剂量反应曲线来研究其功能。我们的结果表明,GPR135在所有分析的组织中均有表达,并且其表达因糖尿病而发生改变,我们还观察到,给予siRNA的糖尿病大鼠对异丙肾上腺素的反应增强。因此,我们得出结论,孤儿受体GPR135在不同组织中表达,其表达因糖尿病而趋于改变,此外它具有功能,似乎与Gi/o蛋白偶联,具有负性变时和变力作用,因此,我们不排除它参与与糖尿病相关的心血管并发症。

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