Abstract: SA-PO302
AQP11 Deficiency Impairs Thymus Development Possibly Through Defective Fat Metabolism
Session Information
- Fluid and Electrolytes: Basic - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid and Electrolytes
- 901 Fluid and Electrolytes: Basic
Authors
- Ishibashi, Kenichi, Meiji Pharmceutical university, Kiyose, Japan
- Sasaki, Sei, Meiji Pharmceutical university, Kiyose, Japan
- Tanaka, Yasuko, Meiji Pharmceutical university, Kiyose, Japan
Background
Aquaporin11 (AQP11) is a superaquaporin permeable to both water and glycerol. AQP11 null mice suffer from polycystic kidneys and die within a month after birth due to uremia. Although AQP11 is expressed widely, it is most abundantly expressed in the thymus and testis. The purpose of this study is to clarify the role of AQP11 in the thymus.
Methods
Immunohistochemistry and microarray analysis with RT-qPCR.
Results
The immunohistochemical analysis revealed the AQP11 expression at the stromal-epithelial cells in the thymus medulla. Surprisingly, the size of the thymus from AQP11 null mice was much smaller than that of the wild mice by half and sometimes by 10%. The vacuolated medullary epithelial cells were observed in the thymus of AQP11 null mice with a normal cortico-medullary structure. The microarray analysis of the gene expression in the thymus was compared between AQP11 null mice and the wild mice by the annotation analysis based on the David Bioinformatics Resources 6.8(beta). We identified 1.5 or more up-regulated 66 genes which mainly participate in the PI3K/Akt signaling pathways to promote metabolism, proliferation, cell survival, growth and angiogenesis. We also found 0.5 or less down-regulated 55 genes, some of which are regulated by the peroxisome proliferator-activated receptor (PPAR) signaling pathway which is activated by fatty acids and their derivatives. RT-qPCR analysis confirmed the enhanced expression of Egfr (Epidermal Growth Factor Receptor), Itgb4 (Integrin beta-4) and Il2ra (interleukin 2 receptor alpha) and the diminished expression of AQP7, Pck1 (Phosphoenolpyruvate carboxykinase 1) and Ucp1 (Mitochondrial uncoupling protein 1). The up-regulated genes for growth signaling may support the survival of the regressed thymus while the down-regulated genes may cause deleterious effects on fat-glucose-energy metabolism in the thymus. The decreased aquaglyceroporin AQP7 in AQP11 null thymus may further compromise the glycerol accumulation leading to the thymus regression.
Conclusion
As the role of AQPs to support memory T cells through glycerol transport has been reported (Cui G et al. Cell. 161:750, 2015), such may also be working in the thymus development. AQP11 may also play an important role in the metabolic control of the thymus.
Funding
- Government Support - Non-U.S.