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Abstract: PO0341

Inhibition of miR-155 Ameliorates AKI by Protecting Telomeres and Reducing DNA Damage of Renal Tubular Cells

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Yin, Qing, Southeast University, Nanjing, Jiangsu, China
  • Wang, Bin, Southeast University, Nanjing, Jiangsu, China
  • Liu, Bi-Cheng, Southeast University, Nanjing, Jiangsu, China
Background

Acute kidney injury (AKI) is associated with significant morbidity and mortality, and currently there is no therapy to prevent or treat established AKI. miR-155 is significantly up-regulated in diabetic nephropathy, IgA nephropathy, bilateral renal ischemia-reperfusion injury (IRI) or drug-induced AKI. However, the molecular mechanism of miR-155 in AKI remains to be studied.

Methods

We subjected miR-155-/- mice and wild-type controls, as well as human proximal tubule cells, to cisplatin-induced AKI models. We assessed kidney function and injury with standard techniques and measured telomere by the fluorescence in situ hybridization.

Results

The expression level of miR-155 was upregulated in both cisplatin-induced AKI mice model and cisplatin-treated HK2 cells. Inhibition of miR-155 expression protected cisplatin-induced AKI both in vivo and in vitro. Compared with wild-type mice, miR-155-/- mice had reduced mortality, improved renal function and pathological damage after cisplatin intervention. Moreover, inhibition of miR-155 expression decreased cells apoptosis and suppressed DNA damage. Additionally, we found that miR-155 efficiently regulates TRF1 expression by targeting a partially conserved sequence motif in the TRF1 3’UTR. Inhibition of miR-155 enhanced the expression of TRF1 and reduced the telomere DNA damage induced by cisplatin. In addition, CDK12 had also been identified as a novel target of miR-155. Inhibition of miR-155 increased the expression of CDK12, and reduced DNA damage and maintain genome stability.

Conclusion

We demonstrated that inhibition of miR-155 ameliorates AKI involving the targeting and regulation of TRF1 and CDK12, indicating a novel regulatory mechanism and elucidating a potential target for cisplatin induced AKI treatment.

Funding

  • Government Support – Non-U.S.