C/EBP homologous protein (CHOP) deficiency ameliorates renal fibrosis in unilateral ureteral obstructive kidney disease.
C/EBP homologous protein (CHOP) deficiency ameliorates renal fibrosis in unilateral ureteral obstructive kidney disease.
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DOI：
10.18632/oncotarget.7870
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Chiang CK
中科院分区：
文献类型：
--
作者：
Liu SH;Wu CT;Huang KH;Wang CC;Guan SS;Chen LP;Chiang CK
无论起始损伤如何，肾小管间质纤维化是慢性肾脏病和终末期肾病的重要致病特征。最近的一项研究表明，CCAAT/增强子结合蛋白（C/EBP）同源蛋白（CHOP）通过氧化应激诱导参与急性缺血/再灌注相关的急性肾损伤。然而，CHOP 对慢性肾脏病相关肾纤维化的影响仍不清楚。在这里，我们研究了 CHOP 在单侧输尿管梗阻 (UUO) 诱导的实验性慢性肾小管间质纤维化中的作用。使用具有或不具有UUO的CHOP敲除小鼠和野生型小鼠。结果表明，UUO处理的野生型小鼠肾脏中肾纤维化标志物胶原蛋白I、纤连蛋白、α-平滑肌肌动蛋白和纤溶酶原激活物抑制剂-1的表达增加，而在UUO处理的CHOP敲除小鼠的肾脏中表达显着减弱。 CHOP 缺乏还可以改善 UUO 肾脏中的脂质过氧化和内源性抗氧化酶消耗、肾小管凋亡和炎症细胞浸润。这些结果表明，CHOP 缺乏不仅可以减轻实验性肾纤维化中的细胞凋亡和氧化应激，还可以减少局部炎症，从而减少 UUO 诱导的肾纤维化。我们的研究结果支持 CHOP 可能是慢性肾病进展中的重要信号分子。
Renal tubulointerstitial fibrosis is an important pathogenic feature in chronic kidney disease and end-stage renal disease, regardless of the initiating insults. A recent study has shown that CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) is involved in acute ischemia/reperfusion-related acute kidney injury through oxidative stress induction. However, the influence of CHOP on chronic kidney disease-correlated renal fibrosis remains unclear. Here, we investigated the role of CHOP in unilateral ureteral obstruction (UUO)-induced experimental chronic tubulointerstital fibrosis. The CHOP knockout and wild type mice with or without UUO were used. The results showed that the increased expressions of renal fibrosis markers collagen I, fibronectin, α-smooth muscle actin, and plasminogen activator inhibitor-1 in the kidneys of UUO-treated wild type mice were dramatically attenuated in the kidneys of UUO-treated CHOP knockout mice. CHOP deficiency could also ameliorate lipid peroxidation and endogenous antioxidant enzymes depletion, tubular apoptosis, and inflammatory cells infiltration in the UUO kidneys. These results suggest that CHOP deficiency not only attenuates apoptotic death and oxidative stress in experimental renal fibrosis, but also reduces local inflammation, leading to diminish UUO-induced renal fibrosis. Our findings support that CHOP may be an important signaling molecule in the progression of chronic kidney disease.
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DOI：
10.1161/hypertensionaha.112.192500
发表时间：
2012-07
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Galán M;Kassan M;Choi SK;Partyka M;Trebak M;Henrion D;Matrougui K
通讯作者：
Matrougui K
影响因子：
5.7
作者：
Chiang, Chih-Kang;Hsu, Shih-Ping;Liu, Shing-Hwa
通讯作者：
Liu, Shing-Hwa
影响因子：
7.3
作者：
Chiang, Chih-Kang;Sheu, Meei-Ling;Liu, Shing-Hwa
通讯作者：
Liu, Shing-Hwa
影响因子：
4.8
作者：
Boergeson, Emma;Docherty, Neil G.;Godson, Catherine
通讯作者：
Godson, Catherine
影响因子：
11.4
作者：
BATCHVAROVA, N;WANG, XZ;RON, D
通讯作者：
RON, D