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MiR-17-5p attenuates kidney ischemia-reperfusion injury by inhibiting the PTEN and BIM pathways.

ABSTRACT:

Background

Kidney ischemia-reperfusion (I/R) injury is an independent risk factor for delayed graft function after kidney transplantation with long-term graft survival deterioration. Previously, we found that the upregulated expression of miR-17-5p exerts a protective effect in kidney I/R injury, but the mechanism has not been clearly studied.

Methods

A kidney I/R injury model was induced in adult C57BL/6 male mice (20-22 g) by clamping both kidney pedicles for 30 min. The miR-17-5p agomir complex was injected into mice 24 h before surgery via the tail vein at a total injection volume of 10 µL/g body weight. The mice were euthanized on post-I/R injury day 2, and kidney function, apoptosis, autophagy, and related molecules were then detected. Human kidney-2 (HK-2) cells, which underwent hypoxia/reoxygenation, were treated with the miR-17-5p agomir, miR-17-5p antagomir, and small interfering ribonucleic acids (siRNAs). Cell viability, apoptosis, autophagy, and molecules were also examined.

Results

Autophagy, miR-17-5p expression, and kidney function damage were significantly more increased in the I/R group than in the sham group. In the cultured HK-2 cells underwent hypoxia/reoxygenation, the miR-17-5p agomir directly inhibited the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Bcl-2 like protein 11 (BIM), and attenuated apoptosis and autophagy. Further, miR-17-5p inhibited autophagy by activating the protein kinase B (Akt)/Beclin1 pathway, which was suppressed by siRNAs. Additionally, the administration of miR-17-5p agomir greatly improved kidney function in the I/R mice group by inhibiting autophagy and apoptosis.

Conclusions

These findings suggest a new possible therapeutic strategy for the prevention and treatment of kidney I/R injury. The upregulation of miR-17-5p expression appears to inhibit apoptosis and autophagy by suppressing PTEN and BIM expression, which in turn upregulates downstream Akt/Beclin1 expression.

SUBMITTER: Ma M

PROVIDER: S-EPMC8576735 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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miR-17-5p attenuates kidney ischemia-reperfusion injury by inhibiting the PTEN and BIM pathways.

Ma Ming M Fu Lei L Jia Zihao Z Zhong Qiang Q Huang Zhongli Z Wang Xianding X Fan Yu Y Lin Tao T Song Turun T

Annals of translational medicine 20211001 20

<h4>Background</h4>Kidney ischemia-reperfusion (I/R) injury is an independent risk factor for delayed graft function after kidney transplantation with long-term graft survival deterioration. Previously, we found that the upregulated expression of miR-17-5p exerts a protective effect in kidney I/R injury, but the mechanism has not been clearly studied.<h4>Methods</h4>A kidney I/R injury model was induced in adult C57BL/6 male mice (20-22 g) by clamping both kidney pedicles for 30 min. The miR-17- ...[more]

PMID: 34790751

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