Abstract: SA-PO445
Essential Roles of Testosterone in Male Kidney Maturation and Repair After Injury
Session Information
- Development and Regenerative Medicine
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Sato, Yuki, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Uchino, Eiichiro, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Oguchi, Akiko, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Kitai, Yuichiro, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan
- Nagamori, Shushi, Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan
- Kanai, Yoshikatsu, Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan
- Murakawa, Yaushiro, RIKEN, Yokohama, Japan
- Yanagita, Motoko, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan
Background
The newborn kidneys are structurally and functionally immature. They mature after birth to adapt to extra-uterine life, yet the comprehensive changes of the kidney have not been defined. We investigated the structural and functional changes in the kidney after weaning and examined the effect of testosterone in this maturation process in male mice.
Methods
We performed phenotypic analysis of mouse kidneys utilizing a combination of histological analysis, bulk transcriptome analysis, charged metabolite analysis by CE-TOFMS and brush border membrane vesicles LC-MS/MS analysis.
Results
Bulk transcriptome analysis of postnatal 3 and 8 week male kidneys showed the gene sets enriched in 8w included those associated with metabolic process and transport in proximal tubule, and structural analysis revealed proximal tubule elongation and hypertrophy in 8 weeks. Most differentially expressed genes (DEGs) identified above were induced between postnatal day 28 and 40, a period of testosterone surge, and were closely correlated with DEGs between adult male and female kidneys. These structural and gene expression changes during maturation were mostly canceled by castration before testosterone surge. Proximal tubules expressed androgen receptor, and some gene expression changes were confirmed in cultured proximal tubules stimulated with testosterone. Consistent results with DEGs were also confirmed at protein levels and related metabolites in vivo. For instance, induction of cystine transporter SLC7A13 expression as well as the increase in cysteine and cysteine-glutathione disulphide-Divalent in the kidney were confirmed in this period. Fatty acid b-oxidation enzymes were also increased during this period. Some of the down-regulated genes across puberty were reactivated after injury and returned back with repair.
Conclusion
Proximal tubules are the main site of maturation after weaning and acquire the ability to absorb and metabolize a variety of filtered substances and increase energy metabolism, which were mainly driven by testosterone.
Funding
- Government Support - Non-U.S.