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不同类型实验性高血压大鼠肾上腺中的Wnt/β-连环蛋白信号传导

Wnt/β-catenin signaling in the adrenal glands of rats in various types of experimental hypertension.

作者信息

Kasacka Irena, Piotrowska Żaneta, Domian Natalia, Lewandowska Alicja

机构信息

1Department of Histology and Cytophysiology, Medical University of Białystok, Białystok, Poland.

出版信息

Endocr Connect. 2022 Jul 19;11(8). doi: 10.1530/EC-22-0121. Print 2022 Aug 1.

Abstract

Wnt/β-catenin signaling plays a key role in maintaining homeostasis, which is disturbed in hypertension. Taking into account the lack of literature describing changes in the Wnt/β-catenin pathway in the adrenal glands under conditions of elevated arterial pressure, here we compare the expression of WNT4, WNT10A, β-catenin, and GSK-3β in the adrenal glands of hypertensive rats of various etiologies. The studies were carried out on the adrenal glands of rats with spontaneous hypertension (SHR), renalvascular (2K1C), and deoxycorticosterone acetate (DOCA)-salt. Immunohistochemical and PCR methods were used to identify the molecular components of the canonical signaling pathway and to evaluate gene expression. Immunoreactivity and expression of WNT4, WNT10A, β-catenin, and GSK-3β in adrenals of SHR was decreased, compared to control rats. In adrenals of 2K1C rats, intensity of immunohistochemical reaction and expression of WNT4 and β-catenin was lower, while immunoreactivity and expression of WNT10A and GSK-3β were higher, compared to normotensive animals. Significantly stronger immunoreaction and expression of WNT4, β-catenin and GSK-3β but weaker immunoreactivity and expression of WNT10A were noted in adrenals in DOCA-salt rats, compared to control rats. In conclusion, our data provide new molecular information indicating that the canonical WNT pathway is disrupted in the adrenal glands of hypertensive rats. They show that the dysregulation of the WNT pathway depends on the etiology of hypertension.

摘要

Wnt/β-连环蛋白信号通路在维持体内平衡中起关键作用,而在高血压状态下该平衡会受到干扰。鉴于缺乏关于动脉血压升高情况下肾上腺中Wnt/β-连环蛋白通路变化的文献描述,在此我们比较了不同病因的高血压大鼠肾上腺中WNT4、WNT10A、β-连环蛋白和GSK-3β的表达。研究在自发性高血压大鼠(SHR)、肾血管性高血压大鼠(2K1C)和醋酸脱氧皮质酮(DOCA)-盐诱导的高血压大鼠的肾上腺上进行。采用免疫组织化学和PCR方法来鉴定经典信号通路的分子成分并评估基因表达。与对照大鼠相比,SHR肾上腺中WNT4、WNT10A、β-连环蛋白和GSK-3β的免疫反应性和表达降低。与血压正常的动物相比,2K1C大鼠肾上腺中WNT4和β-连环蛋白的免疫组织化学反应强度和表达较低,而WNT10A和GSK-3β的免疫反应性和表达较高。与对照大鼠相比,DOCA-盐大鼠肾上腺中WNT4、β-连环蛋白和GSK-3β的免疫反应和表达明显更强,但WNT10A的免疫反应性和表达较弱。总之,我们的数据提供了新的分子信息,表明经典WNT通路在高血压大鼠的肾上腺中被破坏。它们表明WNT通路的失调取决于高血压的病因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8a8/9346341/75e0dac3333f/EC-22-0121fig1.jpg

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