Thioredoxin-interacting protein promotes renal fibrosis in mice by inducing oxidative stress

Qirui HE; Yang LI; Wenzhen DENG; Dongfang LIU

doi:10.16016/j.1000-5404.201805196

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Thioredoxin-interacting protein promotes renal fibrosis in mice by inducing oxidative stress

Basic Medicine | 更新时间：2026-01-09

- Thioredoxin-interacting protein promotes renal fibrosis in mice by inducing oxidative stress
- Journal of Third Military Medical University Vol. 40, Issue 22, Pages: 2061-2067(2018)
- 作者机构：
  
  400010 重庆, 重庆医科大学附属第二医院内分泌科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81370467);the Scientific Research Project of Chongqing Municipal Health and Family Planning Committee(2016ZDXM011);the Science and Technology Innovation Special Project of Social Undertakings and People's Livelihood Security of Chongqing(CSTC2017shmsA130069)
- DOI：10.16016/j.1000-5404.201805196
  CLC： R341;R363.21;R692
- Received：15 May 2018，
  
  Revised：2018-08-06，
  
  Published：30 November 2018
- 稿件说明：
移动端阅览
Qirui HE, Yang LI, Wenzhen DENG, et al. Thioredoxin-interacting protein promotes renal fibrosis in mice by inducing oxidative stress[J]. Journal of Third Military Medical University, 2018, 40(22): 2061-2067.
DOI：

Qirui HE, Yang LI, Wenzhen DENG, et al. Thioredoxin-interacting protein promotes renal fibrosis in mice by inducing oxidative stress[J]. Journal of Third Military Medical University, 2018, 40(22): 2061-2067. DOI： 10.16016/j.1000-5404.201805196.

摘要

目的

探讨硫氧还蛋白相互作用蛋白(thioredoxin interaction protein

TXNIP)对肾脏纤维化的作用。

方法

将12只SPF级C57BL/6J小鼠和12只TXNIP基因敲除鼠(TXNIP

-/-

)均按随机数字表法分为2组：正常对照组(normal control group

NC组)和高脂饮食组(high-fat diet group

HFD组)，喂养16周后取其肾组织，用HE、PAS及Masson染色方法观察肾脏组织病理变化及纤维化改变，采用免疫荧光法检测α-平滑肌肌动蛋白(α-SMA)在肾脏组织的表达水平，并通过Western blot检测肾脏组织中TXNIP、TGF-β1、α-SMA、p38 MAPK及p-p38 MAPK的表达情况。

结果

NC组与HFD组中TXNIP

-/-

小鼠的肾脏纤维化程度及p-p38 MAPK蛋白表达水平均明显低于C57BL/6J小鼠(

0.05)；而C57BL/6J小鼠HFD组与NC组相比，TXNIP在肾脏表达明显上调，且肾脏纤维化及p38磷酸化水平明显增加(

0.05)。

结论

硫氧还蛋白相互作用蛋白可能促进高脂诱导下肾脏纤维化，其作用机制可能与激活p38 MAPK信号通路有关。

Abstract

Objective

To investigate the role of thioredoxin-interacting protein (TXNIP) in high-fat diet-induced renal fibrosis.

Methods

Specific pathogen-free C57BL/6J mice and TXNIP knockout mice (TXNIP

-/-

) were both randomly divided into normal control group and high-fat diet group. After 16 weeks of feeding

the mice were sacrificed and the kidneys were dissected to observe the pathological changes and fibrotic changes using HE

PAS and Masson staining. The expression of α-smooth muscle actin (α-SMA) in the renal tissue was detected using immunofluorescence assay; Western blotting was used to detect the expression of TXNIP

α-SMA

transforming growth factor-β1 (TGF-β1)

p38 mitogen

-activated protein kinase (p38 MAPK) and its phosphorylation (p-p38 MAPK) in the renal tissue.

Results

TXNIP

-/-

mice fed on both normal and high-fat diet showed significantly lower expression levels of p-p38 MAPK and milder renal fibrosis than C57BL/6J mice (

0.05). Compared with the normal control mice

C57BL/6J mice fed on high-fat diet had significantly increased expression of TXNIP and p-p38 MAPK in the kidneys and more obvious renal fibrosis (

0.05).

Conclusion

TXNIP plays a role in promoting renal fibrosis in mice fed on high-fat diet

and its mechanism may involve the activation of p38 MAPK signaling pathway.

关键词

Keywords

references

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