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MiR-194 targets Runx1/Akt pathway to reduce renal fibrosis in mice with unilateral ureteral obstruction

International Urology and Nephrology volume 52, pages 1801–1808 (2020)Cite this article

Abstract

Purpose

Chronic kidney disease (CKD) has become a global public health problem and accompanied by renal fibrosis. MiR-194, a tumor suppressor gene, has been previously reported to be associated with the pathogenesis of tissue fibrosis. However, the role of miR-194 in the pathogenesis of renal fibrosis remains unknown.

Methods

A renal fibrosis model was constructed by unilateral ureteral obstruction (UUO) in male C57BL/6 mice. HE and MASSON stainings were used for histological analysis. The expression level of miR-194 was detected by RT-qPCR. The protein expression was detected by western blotting. The levels of inflammatory cytokines were detected by ELISA. The relationship between miR-194 and Runx1 was further verified by dual luciferase reporter assay.

Results

The results showed that miR-194 level was downregulated in kidney tissue of UUO mice, accompanied by significantly pathological damage and renal fibrosis. MiR-194 mimics significantly reduced pathological damage and alleviated renal fibrosis that caused by UOO, and inhibited the expression levels of α-SMA and collagen I. In addition, miR-194 mimics also reduced the expression level of serum inflammatory factors. Moreover, in vitro analysis indicated that Runx1 was a downstream target gene of miR-194. Furthermore, mechanism analysis indicated that miR-194 reduced mouse renal fibrosis by inhibiting the Runx1/AKT pathway in vivo and in vitro.

Conclusion

The present findings suggested that miR-194 targets Runx1/Akt pathway to reduce renal fibrosis in UOO-induced mice. This study provides a novel strategy for the prevention and treatment of renal fibrosis.

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Abbreviations

CKD:

Chronic kidney disease

UUO:

Unilateral ureteral obstruction

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Funding

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Affiliations

  1. Department of Nephrology, Hubei Province, Wuhan No. 1 Hospital, 215# Zhongshan Avenue, Wuhan, 430022, China

    Li Cheng, Can Tu, Yonglong Min, Da He, Sheng Wan & Fei Xiong

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  1. Li Cheng
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  2. Can Tu
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  3. Yonglong Min
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  4. Da He
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  6. Fei Xiong
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Contributions

LC and FX conceived and designed the experiments, CT and YLM analyzed and interpreted the results of the experiments, DH and SW performed the experiments

Corresponding author

Correspondence to Fei Xiong.

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Conflict of interest

The authors declare that they have no competing interests, and all authors confirm its accuracy.

Ethics approval

The animal use protocol listed below has been reviewed and approved by the Animal Ethical and Welfaer Committee. Approval No. 2019–802.

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Cheng, L., Tu, C., Min, Y. et al. MiR-194 targets Runx1/Akt pathway to reduce renal fibrosis in mice with unilateral ureteral obstruction. Int Urol Nephrol 52, 1801–1808 (2020). https://doi.org/10.1007/s11255-020-02544-5

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  • DOI: https://doi.org/10.1007/s11255-020-02544-5

Keywords

  • miR-194
  • Renal fibrosis
  • Inflammation
  • Runt-related transcription factor 1
  • Protein kinase B