Abstract: TH-OR083
CD44 Impacts Glomerular Parietal Epithelial Cell Changes in the Aged Mouse Kidney
Session Information
- Glomerular Diseases: Fibrosis and Extracellular Matrix
November 07, 2019 | Location: Salon C, Walter E. Washington Convention Center
Abstract Time: 05:30 PM - 05:42 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Hamatani, Hiroko, University of Washington, Seattle, United States
- Eng, Diana G., University of Washington, Seattle, Washington, United States
- Hiromura, Keiju, Gunma University Graduate School of Medicine, Maebashi, Japan
- Pippin, Jeffrey W., University of Washington, Seattle, Washington, United States
- Shankland, Stuart J., University of Washington, Seattle, Washington, United States
Background
CD44, an activated parietal epithelial cell (PEC) marker, increases with aging, and colocalizes with pERK to increase extracellular matrix and epithelial-mesenchymal transition (EMT). The purpose of the current study was to determine the effect of CD44 on PECs with aging.
Methods
CD44 knockout and wildtype control mice at 4 or 24 months were used in this study. Immunohistochemistry and immunofluorescence staining were performed and glomeruli were assessed as follows; outer cortex (OC) vs. juxta-medulla (JM), young vs. aged, and wildtype (WT) vs. CD44 knockout (KO).
Results
Aged WT mice had an increase in segmental and global glomerulosclerosis in JM glomeruli, whereas aged CD44KO mice did not develop either segmental or global glomerulosclerosis. Bowman’s capsule length increased with age and was longer in JM than in OC glomeruli. It was significantly less in aged CD44KO mice compared with WT mice in both OC (212.4±11.7µm vs. WT, 252.4±16.5µm, P<0.0001) and JM glomeruli (325.1±24.0µm vs. 373.1±32.2µm, P<0.0001). In WT mice, PEC number was higher in JM versus OC glomeruli, and was increased with age in JM glomeruli, while knockout of CD44 prevented this aged-related increase. PEC density was higher in JM than in OC glomeruli, and was lower in aged mice than in young mice, however there was no significant difference between WT and CD44KO mice. Glomerular tuft area was larger in JM than in OC and was significantly less in aged CD44KO mice versus WT mice, in both OC (2801±241µm2 vs. 4415±379µm2, P<0.0001) and JM glomeruli (6011±823µm2 vs. 8391±892µm2, P<0.0001). Podocyte number was higher in aged CD44KO mice versus WT mice in JM glomeruli. Podocyte density was higher in aged CD44KO versus WT mice in both OC and JM glomeruli. The expression of EMT markers, α-SMA and vimentin, and activated form of ERK (pERK) and a downstream target of mTOR, pS6RP was increased in aged WT mice especially in JM glomeruli, and was decreased in CD44KO mice.
Conclusion
We showed that knockout of CD44 attenuated age-related increase of glomerulosclerosis, Bowman’s capsule length, glomerular hypertrophy, pERK, pS6RP, and EMT marker expression. Our data suggest that CD44 is involved in aged-related changes of glomeruli and CD44 is associated with activation of ERK and mTOR signaling.
Funding
- NIDDK Support