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β-连环蛋白依赖性信号通路促成高血压大鼠的肾纤维化。

β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats.

作者信息

Cuevas Catherina A, Tapia-Rojas Cheril, Cespedes Carlos, Inestrosa Nibaldo C, Vio Carlos P

机构信息

Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile.

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Alameda 340, 8331150 Santiago, Chile.

出版信息

Biomed Res Int. 2015;2015:726012. doi: 10.1155/2015/726012. Epub 2015 Apr 7.

DOI:10.1155/2015/726012
PMID:25945342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4405227/
Abstract

The mechanism of hypertension-induced renal fibrosis is not well understood, although it is established that high levels of angiotensin II contribute to the effect. Since β-catenin signal transduction participates in fibrotic processes, we evaluated the contribution of β-catenin-dependent signaling pathway in hypertension-induced renal fibrosis. Two-kidney one-clip (2K1C) hypertensive rats were treated with lisinopril (10 mg/kg/day for four weeks) or with pyrvinium pamoate (Wnt signaling inhibitor, single dose of 60 ug/kg, every 3 days for 2 weeks). The treatment with lisinopril reduced the systolic blood pressure from 220 ± 4 in 2K1C rats to 112 ± 5 mmHg (P < 0.05), whereas the reduction in blood pressure with pyrvinium pamoate was not significant (212 ± 6 in 2K1C rats to 170 ± 3 mmHg, P > 0.05). The levels of collagen types I and III, osteopontin, and fibronectin decreased in the unclipped kidney in both treatments compared with 2K1C rats. The expressions of β-catenin, p-Ser9-GSK-3beta, and the β-catenin target genes cyclin D1, c-myc, and bcl-2 significantly decreased in unclipped kidney in both treatments (P < 0.05). In this study we provided evidence that β-catenin-dependent signaling pathway participates in the renal fibrosis induced in 2K1C rats.

摘要

高血压诱导肾纤维化的机制尚未完全明确，尽管已经确定高水平的血管紧张素II在其中发挥作用。由于β-连环蛋白信号转导参与纤维化过程，我们评估了β-连环蛋白依赖性信号通路在高血压诱导肾纤维化中的作用。对双肾单夹（2K1C）高血压大鼠给予赖诺普利（10mg/kg/天，共四周）或巴莫酸吡维铵（Wnt信号抑制剂，单次剂量60μg/kg，每3天一次，共2周）治疗。赖诺普利治疗使2K1C大鼠的收缩压从220±4降至112±5mmHg（P<0.05），而巴莫酸吡维铵治疗导致的血压降低不显著（2K1C大鼠从212±6降至170±3mmHg，P>0.05）。与2K1C大鼠相比，两种治疗方法均使未夹闭肾脏中I型和III型胶原蛋白、骨桥蛋白和纤连蛋白水平降低。两种治疗方法均使未夹闭肾脏中β-连环蛋白、p-Ser9-GSK-3β以及β-连环蛋白靶基因细胞周期蛋白D1、c-myc和bcl-2的表达显著降低（P<0.05）。在本研究中，我们提供了证据表明β-连环蛋白依赖性信号通路参与了2K1C大鼠诱导的肾纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/208a2a63198f/BMRI2015-726012.010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/c825d7a6a2dd/BMRI2015-726012.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/043be82e1f54/BMRI2015-726012.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/57cfeff3fb37/BMRI2015-726012.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/dd54e59e68c7/BMRI2015-726012.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/9fe1727cce0e/BMRI2015-726012.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/f2083e668f47/BMRI2015-726012.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/47b087e836ea/BMRI2015-726012.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/642902b17889/BMRI2015-726012.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/2542070f2e9b/BMRI2015-726012.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/208a2a63198f/BMRI2015-726012.010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/c825d7a6a2dd/BMRI2015-726012.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/043be82e1f54/BMRI2015-726012.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/57cfeff3fb37/BMRI2015-726012.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/dd54e59e68c7/BMRI2015-726012.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/9fe1727cce0e/BMRI2015-726012.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/f2083e668f47/BMRI2015-726012.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/47b087e836ea/BMRI2015-726012.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/642902b17889/BMRI2015-726012.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/2542070f2e9b/BMRI2015-726012.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e3f/4405227/208a2a63198f/BMRI2015-726012.010.jpg

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