Abstract: FR-PO073
Retinoic Acid Alleviates Cisplatin Induced Kidney Injury Through Activation of Autophagy
Session Information
- AKI: Tubules, Metabolism, New Models
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Wu, Junxia, Nanjing Medical University, Nanjing, Nanjing, Jiangsu, China
- Wan, Xin, Nanjing First Hospital, Nanjing, China
Background
Retinoic acid (RA) reduces injury, inflammation, and fibrosis in models of acute renal injury, including toxin and ischemia reperfusion AKI, but little is known about its effect on cisplatin induced kidney injury.
Methods
We examine the effects of RA on cisplatin induced kidney injury in vivo and introduce a murine model of cisplatin induced kidney injury by retro-orbital injection of cisplatin both in WT and autophagy-related gene 5–knockout mice. Renal function test, LDH test, HE staining, PCR, immunoblots and immunofluorescence were used in the study. And in vitro, NRK cells were treated with and without cisplatin and were transfected with GFP-LC3 plasmid. Data are representatives of at least three experiments and expressed as means ± SD. Statistical analysis was conducted using the GraphPad Prism software.Statistical differences in multiple groups were determined by multiple comparisons with ANOVA followed by homogeneity test for variance. P<0.05 was considered as significantly different.
Results
Cisplatin group mice exhibited typical features of clinical cisplatin induced kidney injury including renal histology changes, higher level of NGAL and plasm creatinine.In WT mice, RA alleviated cisplatin induced dilation and necrosis of renal tubular epithelial cells and improved renal function and upregulated autophagy. Knockout mice showed more severe kidney injury as was indicated by worsening renal function, more tissue damage. And the protective effect of retinoic acid was not significant in knock out mice as autophagy was blocked. In vitro, RA protected proximal tubular epithelial cells from cisplatin induced injury, inhibited apoptosis and promote the proliferation of epithelial cells after cisplatin induced injury and upregulated autophagy which were confirmed by higher level of LC3 -II / LC3 -I ratio , lower level of P62 by immunoblots and more autophagy punctae after transfection of GFP-LC3 plasmid.
Conclusion
RA alleviates cisplatin-induced kidney injury via upregulating autophagy.
Funding
- Other NIH Support