去乙酰化蛋白酶1在马兜铃酸肾纤维化模型中对TGFβ1/Smad7信号通路的作用

畜牧兽医学报 ›› 2012, Vol. 43 ›› Issue (3): 459-468.

去乙酰化蛋白酶1在马兜铃酸肾纤维化模型中对TGFβ1/Smad7信号通路的作用

杨洋1,2，张中文2*，姚华2，高磊2，李培锋1*，吴国娟2*

1.内蒙古农业大学兽医学院，呼和浩特 010018； 2.北京农学院动物科学技术学院，北京 102206

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2012-03-28 发布日期:2012-03-28
通讯作者: 李培锋1*，吴国娟,张中文

The Role of HDAC1 in the Signal Pathway of TGFβ1 / Smad7 in AAN Model

YANG Yang1,2, ZHANG Zhongwen2*YAO Hua2, GAO Lei2, LI Peifeng1*, WU Guojuan2*

1.College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China; 2.Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China

Received:1900-01-01 Revised:1900-01-01 Online:2012-03-28 Published:2012-03-28
Contact: LI Peifeng1*, WU Guojuan2* ,ZHANG Zhongwen2

摘要/Abstract

摘要： 检测马兜铃酸肾纤维化(AAN)模型肾组织中转化生长因子β1(TGFβ1)、Smad7、去乙酰化蛋白酶1(HDAC1)的mRNA和蛋白表达变化，探讨HADC1和Smad7的表达在AAN发展中的作用及两者间的联系。RTPCR检测TGFβ1、Smad7和HDAC1的mRNA表达，ELASA检测TGFβ1的蛋白表达，免疫组化定位和检测HADC1和Smad7蛋白，HE染色观察肾病理学改变。结果显示：AAN模型肾组织中TGFβ1和HDAC1 mRNA表达呈时间依赖性升高，TGFβ1 mRNA表达较对照组有明显差异(P <0.05)，28 d开始AAN组中HDAC1 mRNA增加,差异极显著(P<0.01)；Smad7 mRNA和蛋白表达均呈下降趋势，HDAC1蛋白免疫组化染色强度呈上调趋势，与对照组比较HDAC1阳性着色主要分布于上皮细胞和间质细胞的细胞核；肾脏病理表现为肾小管浊肿、变性和脱落等急性小管间质损伤，并随用药时间的延长呈进行性加重。本研究表明肾组织中Smad7弱表达可促进TGFβ1信号转导，HDACl mRNA和蛋白在肾组织中的高表达并参与TGFβ1/Smad7信号通路在肾纤维化发展中起重要作用，可能是潜在的新作用靶点。

关键词: AAN, TGFβ1, Smad7, HDAC1

Abstract: The aim of this study was to study the changes in the expression of transforming growth factor β1 (TGFβ1), the TGFβ1 receptor (TβRI), Smad7, and histone deacetylase 1 (HDAC1) in mice with aristolochic acid nephropathy (AAN), and analyze the relationship between HDAC1 and Smad7. RTPCR was applied to detect the mRNA levels of TGFβ1, Smad7 and HDAC1 in kidneys. The TGFβ concentrations were determined by ELISA. HADC1 and Smad7 proteins were localized and detected by immunohistochemistry method. The tissue section technique was used to observe the histopathologic changes, such as kidney damage and renal tubules interstitial fibrosis degree. Results were as follows: In mice with induced AAN, the mRNA levels for TGFβ1and HDAC1 were increased with treatment time. The mRNA levels for TGFβ1 were higher than that of their control (normal mice without treatment) (P<0.05). Starting from 28 day, mRNA of HDAC1 became significantly higher than the level of the control (P<0.01). The levels of Smad7 protein and its mRNA were decreased with time, and lower than that of control. HDAC1 protein expression was increased with time post treatment. Compared with the control group, HDAC1 positive stains were mainly distributed in the epithelial and stromal cell nucleus. Histopathologic changes of kidney showed acute tubular interstitial damage, such as turbidity, swollen, degeneration and fall off of renal tubular. With extension of treatment time, renal tubular damage was aggravated progressively. During the development of AAN in mice, Smad7 can cause renal tubular damage, impare renal tubular renewable repair ability, restrain Smad7 mRNA expression. The weak expression of Smad7 in renal tissues can promote TGFβ1 signal transduction, help the fibre formation and maintain the proliferation condition. One of the mechanism happened is about HDACl, which mRNA and protein high expressions plays an important role in the development aristolochinc acid nephropathy, may be a new potential target.

Key words: aristolochic acid nephropathy, transforming growth factorβ1, Smad7, histone deacetylases 1

杨洋;张中文;姚华;高磊;李培锋;吴国娟. 去乙酰化蛋白酶1在马兜铃酸肾纤维化模型中对TGFβ1/Smad7信号通路的作用[J]. 畜牧兽医学报, 2012, 43(3): 459-468.

YANG Yang;ZHANG ZhongwenYAO Hua;GAO Lei;LI Peifeng;WU Guojuan . The Role of HDAC1 in the Signal Pathway of TGFβ1 / Smad7 in AAN Model[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2012, 43(3): 459-468.

[1]	逄金吉, 白欣洁, 陈顺琪, 蒋无砚, 王子旭, 曹静, 董玉兰, 陈耀星. 单色绿光对鸡胚褪黑激素合成的影响[J]. 畜牧兽医学报, 2017, 48(5): 938-944.
[2]	逄金吉, 白欣洁, 陈顺琪, 蒋无砚, 王子旭, 曹静, 董玉兰, 陈耀星. 单色绿光对鸡胚褪黑激素合成的影响[J]. 畜牧兽医学报, 2017, 48(5): 938-944.
[3]	欧科鹏，李尤简，郭若婷，王颖，顾真真，刘乙，刘小军. 绵羊甲状腺自主合成并分泌褪黑素的研究[J]. 畜牧兽医学报, 2015, 46(4): 576-582.
[4]	欧科鹏，李尤简，郭若婷，王颖，顾真真，刘乙，刘小军. 绵羊甲状腺自主合成并分泌褪黑素的研究[J]. 畜牧兽医学报, 2015, 46(4): 576-582.
[5]	杨洋;张中文;姚华;高磊;李培锋;吴国娟. 去乙酰化蛋白酶1在马兜铃酸肾纤维化模型中对TGFβ1/Smad7信号通路的作用[J]. 畜牧兽医学报, 2012, 43(3): 459-468.