High uric acid induces epithelial-mesenchymal transition of renal tubular epithelial cells <italic style="font-style: italic">via</italic> TLR4/NF-κB signaling pathway

Huifang LIU; Yu XIA; Qian XU; Jiachuan XIONG; Jinghong ZHAO; Yongnian LI

doi:10.16016/j.1000-5404.201704023

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High uric acid induces epithelial-mesenchymal transition of renal tubular epithelial cells via TLR4/NF-κB signaling pathway

Basic Medicine | 更新时间：2026-01-09

- High uric acid induces epithelial-mesenchymal transition of renal tubular epithelial cells via TLR4/NF-κB signaling pathway
- Journal of Third Military Medical University Vol. 39, Issue 19, Pages: 1919-1925(2017)
- 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：
- 基金信息：
- DOI：10.16016/j.1000-5404.201704023
  CLC： R322.61;R329.2;R446.122
- Received：09 April 2017，
  
  Revised：2017-04-18，
  
  Published：15 October 2017
- 稿件说明：
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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：

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

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

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

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(

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(

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

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

To determine the effect of epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells induced by uric acid

and investigate the underlying mechanism.

Methods

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

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 (

0.05). High dose of uric acid enhanced the expression levels of IL-1β and TNF-α (

0.05) and induced activation of TLR4/NF-κB signaling pathway in HK-2 cells (

0.05). Targeted inhibition of NF-κB signaling pathway significantly suppressed EMT induced by uric acid in HK-2 cells.

Conclusion

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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⁰

High uric acid induces epithelial-mesenchymal transition of renal tubular epithelial cells via TLR4/NF-κB signaling pathway

DOI：10.16016/j.1000-5404.201704023

摘要

Abstract

关键词

Keywords

references