Abstract: FR-PO179
Irisin Modulates Renal Ischemia-Reperfusion Injury by Upregulating Mitochondrial Autophagy Marker Protein LC3
Session Information
- AKI: Mechanisms - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Yu, Cui, Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Background
Acute kidney injury (AKI) is a clinical syndrome with a high incidence and increased cost and mortality for hospitalized patients, and are still lacking of effective therapeutic drugs. Irisin has been reported to have inhibitory effects on cellular inflammation, reduced cell apoptosis, and antioxidant stress in various diseases. But it is still unknown whether Irisin has therapeutic effects after ischemic AKI.
Methods
We evaluated the serum Irisin levels and their correlation with renal function in AKI patients and healthy control groups. We constructed a mice model of ischemia-reperfusion(I/R) kidney injury and administered exogenous Irisin toinvestigated the potential therapeutic effects and mechanisms through a series of experimental techniques such as renal tubular microperfusion.
Results
We found that the Scr level in the AKI patient was significantly higher thanthat in the healthy control group (256.8 ± 30.5 vs 61.9 ± 10.5 umol/L, P<0.0001), the BUN level was significantly higher (17.1 ± 6.5 vs 5.1 ± 1.0 mmol/L, P<0.0001), and the Irisin level was significantly reduced (39.9 ± 8.2 vs 76.7 ± 13.8 ng/ml, P<0.0001). We found that exogenous Irisin reduced the renal damage indicators in mice model. The stability of mitochondrial JC-1 membrane potential increased and the ROS decreased after H/R in the Irisin treatment group. Irisin up-regulated the expression of renal mitochondrial autophagy related proteins PINK1 and PARK2 and marker protein LC3, enhanced mitochondrial autophagy, and down regulated the activation of NLRP3 inflammasome.
Conclusion
This study suggests that Irisin may serve as a potential biomarker of ischemic AKI. Irisin has therapeutic effects on renal IRI, and its protective effect may be related to enhancing mitochondrial autophagy by upregulating mitochondrial autophagy marker protein LC3. This study provides theoretical support for Irisin as a therapeutic drug for ischemic AKI.
Hypothesis of the mechanism by which Irisin alleviates renal ischemia-reperfusion injury
Funding
- Government Support – Non-U.S.