Abstract: SA-PO062
Mitochondrial Fission and Apoptosis-Related CircRNA Plays an Important Role in Ischemia-Reperfusion-Induced AKI by Sponging miR-652-3p
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
- Ran, Mengping, The Affiliated Shengjing Hospital of China Medical University, Shenyang, China
- Luan, Junjun, The Affiliated Shengjing Hospital of China Medical University, Shenyang, China
- Zhou, Hua, The Affiliated Shengjing Hospital of China Medical University, Shenyang, China
Background
Circular RNAs (circRNAs) can serve as sponges of microRNAs (miRs) to participate in the pathogenesis of various diseases. A study reports that mitochondrial fission and apoptosis-related circRNA (MFACR) mediates cardiomyocyte apoptosis by sponging miR-652-3p to regulate mitochondrial fission process 1 (MTFP1) pathway. However, the role of MFACR in acute kidney injury (AKI) remains unclear. We aim to investigate whether MFACR is involved in ischemia and reperfusion (I/R)- induced AKI and its corresponding mechanisms.
Methods
Male Balb/c mice were subjected to 35 mins of bilateral renal ischemia and then reperfusion. We evaluated AKI by examining blood urea nitrogen (BUN), tubular necrosis with PAS and spoptosis by TUNEL staining, and renal inflammation by measuring interleukin-6 (Il6) and tumor necrosis factor-α (Tnfα) 48h after the reperfusion. Meanwhile, we examined the expression of mitochondria related mRNAs and proteins including optic atrophy 1 (OPA1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), and mitochondrial transcription factor A (TFAM). Finally, we measured the levels of MFACR, miR-652-3p, and Mtfp1. We analyzed the match seeds between MFACR and miR-652-3p as well as miR-652-3p and Mtfp1 with TargetScan and miRanda.
Results
We found that kidney function declined with elevated BUN levels, increased renal tubular necrosis scores on PAS and positive apoptosis on TUNEL staining in kidneys 48h after I/R in mice compared to the shamed control mice. Il6 elevated 14-folds and Tnfα elevated about 5-folds in I/R mice compared to shamed mice. Renal mitochondrial damage biomarkers including OPA1, PGC-1α, TFAM statistically decreased in I/R mice on the levels of their mRNAs and proteins. Importantly, renal MFACR was downregulated, miR-652-3p was upregulated, and Mtfp1 was downregulated in I/R-induced mice compared to the shamed mice. Finally, we found perfect match seeds between MFACR and miR-652-3p as well as between miR-652-3p and Mtfp1 on TargetScan and miRanda analysis.
Conclusion
Our findings suggested that MFACR played an important role in I/R induced AKI. The mechanism might be that MFACR regulates renal mitochondrial functions by sponging miR-652-3p and consequently increasing MTFP1. Regulating MFACR-miR-652-3p-MTFP1 pathway may open a novel therapeutic avenue for AKI.
Funding
- Government Support - Non-U.S.