Abstract: PO0341
Inhibition of miR-155 Ameliorates AKI by Protecting Telomeres and Reducing DNA Damage of Renal Tubular Cells
Session Information
- AKI: Mechanisms of Injury
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
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.