Abstract: SA-PO108
miR-214 Promotes Mitochondrial Fragmentation and Cellular Apoptosis by Targeting MFN2 in ATP-Depleted Renal Proximal Tubular Cells
Session Information
- AKI: Mechanisms - Primary Injury and Repair - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Yan, Yu, Augusta University, Augusta, Georgia, United States
- Dong, Zheng, Medical College of Georgia, Augusta, Georgia, United States
Background
Mitochondria injury is a pathological factor for AKI by promoting cell apoptosis. microRNAs have been reported to play important regulatory roles in AKI. However, microRNA associated with mitochondrial injuries are poorly understood.
Methods
Azide-induced ATP-depletion model to study AKI in renal proximal tubular cells (RPTCs) in vitro. The mRNA expressions of miR-214 were detected by RT-qPCR .The protein levels of MFN2,β-actin and cleaved-caspase3 were determined by western blot, then analysis by image J. The mitochondria morphology was detected by confocal microscope.
Results
We found that miR-214 level was upregulated after azide treatment and reperfusion in RPTCs, while MFN2 protein level was reduced. Overexpression of miR-214 by transfection decreased MFN2 protein level. The inhibition of miR-214 by anti-miR-214 LNA reduced the decrease in MFN2 and induced by ATP depletion, and the percentage of RPTCs with fragmented mitochondria were decreased as well. The number of apoptotic cells and the increase in cleaved-caspase 3 expression induced by azide treatment in RPTCs were reduced by anti-miR-214 LNA transfection. On the contrary, overexpression of miR-214 increased apoptosis and cleaved-caspase 3 expression in ATP-depleted RPTCs.
Conclusion
These results suggest that miR-214 upregulation promotes mitochondrial fragmentation and cellular apoptosis by downregulating MFN2 expression and inhibition of miR-214 ameliorates mitochondrial fragmentation and reduces cellular apoptosis by upregulating MFN expression in ATP-depleted RPTCs. Targeting miR-214 could show potentially therapeutic effect in AKI.
Funding
- NIDDK Support