Abstract: PO0157
VNN1 Mediates Renal Maladaptive Repair After AKI by Inducing Premature Senescence of Renal Tubular Cells
Session Information
- AKI Mechanisms - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Chen, Kehong, Daping hospital, Chongqing, Chongqing, China
Background
Renal maladaptive repair can promote lead to the transition of acute kidney injury (AKI) to chronic kidney disease. Sustained renal interstitial damage caused by accelerated senescence of renal tubular cells leads to renal fibrosis after AKI. Vanin-1 (VNN1) is an extracellular enzyme with panthenylmethylaminease activity that indirectly reduces the synthesis of glutathione, causing oxidative stress. This study aimed at investigating the role of VNN1 in senescence of renal tubular cells after renal ischemia reperfusion (I/R) injury.
Methods
Thirty male wild BALB/c mice were randomly divided into control group, sham group and I/R group. In the I/R group, bilateral renal pedicles were clamped for 35 min and reperfusion was performed. The expression of VNN1 were detected. Furthermore, the degree of renal damage and the senescence of renal tubular cells were compared in wild type mice and VNN1 knockout mice after I/R injury.
Results
Scr, BUN and renal injury score increased significantly at the early stage (3d) of renal injury after I/R. Renal fibrosis was observed in the advanced stage (28-42d). The expression of VNN1 in renal tubular cells of I/R group increased after I/R injury. The SCr, BUN levels in VNN1 KO mice were significantly lower than those in wild type mice at 7-28 d after renal reperfusion. The renal interstitial fibrosis level was significantly higher in VNN1 KO mice than that of wild type mice at 42d after reperfusion. The results suggest that VNN1 KO promotes renal repair of AKI. It is found that 50% of the VNN1 up-regulated genes after IR renal injury were stress-related genes through mRNA microarray analysis. The ratio of P16 positive tubule cells in VNN1 KO mice was significantly higher than that in wild-type mice at 7d after renal reperfusion. The expression levels of phosphorylated RB1 in VNN1 KO renal tubular cells were significantly higher than those in the wild type renal tubular cells after hypoxia/reoxygenation, suggesting that VNN1 could promote the senescence of renal tubule cells through P16- RB1 pathway during AKI repair
Conclusion
VNN1 mediates renal maladaptive repair after AKI by inducing premature senescence of renal tubular cells through P16-RB1 pathway.
Funding
- Government Support - Non-U.S.