Abstract: SA-PO1012
Notch Signaling and Adam10 in Lithium-Induced Collecting Duct Remodeling in Mouse Kidney
Session Information
- Fluid and Electrolytes: Basic - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid and Electrolytes
- 901 Fluid and Electrolytes: Basic
Authors
- Zhang, Yue, Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
- Peti-Peterdi, Janos, University of Southern California, Los Angeles, California, United States
- Roedel, Marshall R., Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
- Liu, Tao, Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
- Riquier-brison, Anne, University of Southern California, Los Angeles, California, United States
- Carlson, Noel G., Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
- Kishore, Bellamkonda K., Univ. of Utah and VA Medical Center, Salt Lake City, Utah, United States
Background
The cell biology of lithium (Li) induced collecting duct (CD) remodeling, whereby the percent of AQP2-positive principal cells (PC) is decreased with a proportionate increase in [H+]-ATPase-positive intercalated cells (IC), is not well defined. It has been reported that genetic suppression of Notch signaling or Adam10 interferes with the development of CD resulting in off-spring with very low percentage of PC in the kidney. Hence, here we evaluated whether these two play a similar role in Li-induced CD remodeling in adult mice.
Methods
Groups of mice (B6D2; N = 5/group) were fed either a regular or LiCl-containing chow for 30 days and humanely euthanized. Using confocal immunofluorescence microscopy and double labeling, kidney sections were examined for the percent of AQP2 or [H+]-ATPase positive cells. cDNA prepared from the medulla was subjected to Notch signaling PCR Array, and expression of selected genes was further confirmed by real-time PCR on all samples.
Results
Li treatment caused significant polyuria associated with a significant decrease in percentage of PC in the medulla (88.2 ± 3.4 vs. 69.2 ± 0.8, P < 0.05), and a proportionate increase in the percentage of IC (11.3 ± 3.4 vs. 30.0 ± 0.8, P < 0.05). Several genes were under or over expressed in Li-treated mice (Table).
Conclusion
Similar to its role during embryonic life, Notch signaling plays a role in Li-induced CD remodeling. However, our results do not support a role for Adam10 in Li-induced CD remodeling in adult mice. The roles of Nr4a2, Neurla1A and Figf in CD remodeling need to be further defined.
Expression of Genes in Li-treated Mice
| Gene | Name | Change* |
| Notch1 | Notch gene homolog 1 | 19 |
| Notch 2 | Notch gene homolog 2 | 28 |
| Notch 3 | Notch gene homolog 3 | 16 |
| Notch4 | Notch gene homolog 4 | 15 |
| Jag2 | Jagged 2 | 23 |
| Dll1 | Delta-like 1 | 34 |
| Runx1 | Runt related transcription factor 1 | 27 |
| cdkn1a | cyclin-dependent kinase inhibitorr 1A (P21) | 29 |
| Nr4a2 | Nuclear receptor subfamily 4, group A, member 2 | 619 |
| Neurla1A | Neutralized homolog 1A | 839 |
| Figf | C-fos induced growth factor | 1119 |
| Adam10 | A disintegrin and metallopeptidase domain 10 | 500 |
*Percent of the mean values in the control diet-fed group
Funding
- NIDDK Support