β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats.
β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats.
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DOI：
10.1155/2015/726012
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发表时间：
2015
影响因子：
--
通讯作者：
Vio CP
中科院分区：
文献类型：
--
作者：
Cuevas CA;Tapia-Rojas C;Cespedes C;Inestrosa NC;Vio CP
高血压引起的肾脏纤维化的机制还不是很清楚，尽管已经确定高水平的血管紧张素II参与了这一效应。由于β-连环蛋白信号转导参与了纤维化过程，我们评估了β-连环蛋白依赖的信号转导通路在高血压诱导的肾纤维化中的作用。两肾一夹(2K1C)高血压大鼠给予赖诺普利(10 mg/kg/d，共4周)或氨甲酸吡啶(Wnt信号抑制剂，单次剂量60 /kg，每3天1次，共2周)治疗。赖诺普利可使2K1C大鼠的收缩压由2K1C大鼠的2 2 0±4降至112±5 (P<0.0 5)，而氨甲酸丙戊酯的降压作用不明显(2 2 1±6降至170±3 mm HgP>；0.0 5)。与2K1C大鼠相比，两组大鼠未夹肾的I型和III型胶原、骨桥蛋白和纤维连接蛋白水平均降低。β-catenin、p-Ser9-GSK-3β和β-catenin靶基因cyClind1、c-myc和bcl2在两组大鼠未夹肾组织中的表达均显著降低(P<0.05)。本研究为β-连环蛋白依赖的信号通路参与2K1C大鼠肾脏纤维化提供了证据。
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.
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影响因子：
3.4
作者：
Ge WS;Wang YJ;Wu JX;Fan JG;Chen YW;Zhu L
通讯作者：
Zhu L
影响因子：
8.3
作者：
GUAN, S;FOX, J;NAVAR, LG
通讯作者：
NAVAR, LG
影响因子：
24
作者：
Collins, AR;Schnee, J;Hsueh, WA
通讯作者：
Hsueh, WA
DOI：
10.1111/j.1524-6175.2005.05111.x
发表时间：
2006-03-01
期刊：
Journal of clinical hypertension (Greenwich, Conn.)
影响因子：
--
作者：
Griffin, Karen A
通讯作者：
Griffin, Karen A
DOI：
10.1152/ajprenal.00429.2014
发表时间：
2015-02-15
影响因子：
4.2
作者：
Cuevas, Catherina A.;Gonzalez, Alexis A.;Prieto, Minolfa C.
通讯作者：
Prieto, Minolfa C.