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高尿酸通过TLR4/NF-κB信号通路诱导肾小管上皮细胞上皮-间充质转化的作用研究
High uric acid induces epithelial-mesenchymal transition of renal tubular epithelial cells
via TLR4/NF-κB signaling pathway- 第三军医大学学报 2017年39卷第19期 页码：1919-1925
- 作者机构：
1.550004 贵阳，贵州医科大学基础医学院免疫教研室
2.400037 重庆，第三军医大学新桥医院肾内科，全军肾脏病中心
- 作者简介：
[ 李永念，E-mail：lyn@gmc.edu.cn LI Yongnian, E-mail:lyn@gmc.edu.cn
- 基金信息：
DOI：10.16016/j.1000-5404.201704023
中图分类号： R322.61;R329.2;R446.122收稿：2017-04-09，
修回：2017-04-18，
纸质出版：2017-10-15
- 稿件说明：
移动端阅览
刘会芳, 夏雨, 徐倩, 等. 高尿酸通过TLR4/NF-κB信号通路诱导肾小管上皮细胞上皮-间充质转化的作用研究[J]. 第三军医大学学报, 2017,39(19):1919-1925.
Huifang LIU, Yu XIA, Qian XU, et al. High uric acid induces epithelial-mesenchymal transition of renal tubular epithelial cells
via TLR4/NF-κB signaling pathway[J]. Journal of Third Military Medical University, 2017, 39(19): 1919-1925.刘会芳, 夏雨, 徐倩, 等. 高尿酸通过TLR4/NF-κB信号通路诱导肾小管上皮细胞上皮-间充质转化的作用研究[J]. 第三军医大学学报, 2017,39(19):1919-1925. DOI： 10.16016/j.1000-5404.201704023.
Huifang LIU, Yu XIA, Qian XU, et al. High uric acid induces epithelial-mesenchymal transition of renal tubular epithelial cells
via TLR4/NF-κB signaling pathway[J]. Journal of Third Military Medical University, 2017, 39(19): 1919-1925. DOI： 10.16016/j.1000-5404.201704023.
摘要
目的
2
探讨尿酸诱导肾小管上皮细胞上皮-间充质细胞转化(epithelia-mesenchymal transition，EMT)的作用及机制。
方法
2
采用不同质量浓度的尿酸预孵育肾小管上皮细胞(HK-2)48 h，通过倒置显微镜观察尿酸对HK-2细胞形态的影响，Western blot检测Fibronectin、α-SMA和E-cadherin蛋白表达变化。Real-time PCR检测炎症因子IL-1β、IL-6以及TNF-α mRNA的表达变化，免疫荧光检测上皮细胞标志物cytokeratin和间充质细胞标志物vimentin的表达变化。
结果
2
与正常组相比，15 mg/dL的尿酸处理HK-2细胞48 h后，HK-2细胞间隙增
大，呈长梭形改变。间充质细胞标志物Fibronectin、α-SMA表达明显升高，而上皮细胞标志物E-cadherin的表达明显下降(
P
<
0.05)。同时，高浓度尿酸诱导了HK-2细胞炎症因子IL-1β、TNF-α的表达升高(
P
<
0.05)，TLR4/NF-κB信号通路活化，而靶向抑制NF-κB信号通路活化可以显著抑制尿酸诱导的EMT。
结论
2
高尿酸可以通过活化TLR4/NF-κB信号通路诱导肾小管上皮细胞EMT的发生，靶向干预NF-κB信号通路可以显著抑制尿酸诱导的肾间质纤维化。
Abstract
Objective
2
To determine the effect of epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells induced by uric acid
and investigate the underlying mechanism.
Methods
2
Human renal tubular epithelial HK-2 cells were cultured
in vitro
and incubated with different concentrations of uric acid for 48 h. The effects of uric acid on the morphology of HK-2 cells were observed and recorded with the aid of inverted microscope. The protein levels of fibronectin
α-smooth muscle actin (α-SMA) and E-cadherin were detected by Western blotting
while the mRNA expression levels of IL-1β
IL-6 and TNF-α were detected by real-time PCR. Immunofluorescence assay was used to detect the changes of epithelial cell marker cytokeratin and mesenchymal cell marker vimentin.
Results
2
Compared with untreated HK-2 cells
treatment of 15 mg/dL uric acid for 48 h induced the HK-2 cells turned into long-spindled shape
with markedly increased intercellular space. The protein levels of mesenchymal marker fibronectin and α-SMA were significantly increased
while that of the epithelial cell marker E-cadherin was significantly decreased (
P
<
0.05). High dose of uric acid enhanced the expression levels of IL-1β and TNF-α (
P
<
0.05) and induced activation of TLR4/NF-κB signaling pathway in HK-2 cells (
P
<
0.05). Targeted inhibition of NF-κB signaling pathway significantly suppressed EMT induced by uric acid in HK-2 cells.
Conclusion
2
High uric acid induces EMT in renal tubular epithelial cells by activation of the TLR4/NF-κB signaling pathway
and the targeted intervention of NF-κB signaling pathway can significantly suppress uric acid induced renal interstitial fibrosis.
关键词
Keywords
references
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