Abstract: FR-PO359
INO80 Inhibits Tubulointerstitial Apoptosis Under Hypoxia
Session Information
- CKD: Mechanisms - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Miura, Rika, the University of Tokyo School of Medicine, Tokyo, Japan
- Mimura, Imari, the University of Tokyo School of Medicine, Tokyo, Japan
- Sato, Dai, the University of Tokyo School of Medicine, Tokyo, Japan
- Tanaka, Tetsuhiro, the University of Tokyo School of Medicine, Tokyo, Japan
- Nangaku, Masaomi, the University of Tokyo School of Medicine, Tokyo, Japan
Background
Chronic kidney disease (CKD) is known to be caused by various kinds of factors including epigenetic factors. Among them we focused on the role of INO80. INO80 is an ATPase and nucleosome spacing factor. Biological function of INO80 is known to be ATP-dependent chromatin-remodeling, and it regulates transcription, DNA repair and replication. Our aim of this study is to clarify the pathophysiological role of INO80 in the kidney.
Methods
In order to investigate the expression levels of INO80 in the impaired kidney, we utilized 5/6 nephrectomy rats. To clarify the biological function of INO80 in the kidney, we performed in vitro experiments using HK2 (human kidney-2) cells in which INO80 was knocked down by using siRNA. In addition, genome-wide analysis using RNA-seq was performed to identify the downstream target genes of INO80 under hypoxia. Furthermore, we examined the effects of INO80 on apoptosis of tubular cells.
Results
In 5/6 nephrectomy rats, we found that the expression of INO80 was significantly suppressed at the mRNA level compared to sham rats. When HK2 cells were cultured under 1% hypoxic conditions for 24 hours, the expression level of INO80 significantly decreased. Genome-wide analysis by RNA-seq identified 32 downstream target candidate genes whose expressions decreased less than half compared with control siRNA when INO80 was knocked down by siRNA. While, knockdown of INO80 in HK2 cells promoted tubulointerstitial apoptosis by 24 hours, the expression of mRNA of tumor suppressor gene p53 and transcription factor E2F1 was significantly increased.
Conclusion
INO80 plays an important role in suppressing apoptosis in renal tubular cells, and it is considered that E2F1-mediated regulation may be involved in the apoptosis suppression pathway by INO80.