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Published on: August 19, 2020
CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney
Hiroko Hamatani1,2, Diana G Eng1, Keiju Hiromura2
1Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA.
Insights
CD44 in kidney parietal epithelial cells (PECs) drives age-related glomerular changes in mice. Deleting CD44 protected against glomerulosclerosis and preserved podocyte density in aging kidneys.
Area of Science:
- Nephrology
- Gerontology
- Cell Biology
Background:
- CD44 is implicated in parietal epithelial cell (PEC) activation.
- CD44 expression increases in PECs of aged mice, but its role is unclear.
- Understanding CD44's function in aging kidneys is crucial for age-related kidney disease research.
Purpose of the Study:
- To investigate the biological role of CD44 in PECs during healthy aging in mice.
- To determine if CD44 influences age-related changes in glomerular structure and function.
- To explore the involvement of ERK and mTOR signaling pathways.
Main Methods:
- Comparison of young and aged CD44 knockout (CD44-/-) and wild-type (CD44+/+) mice.
- Assessment of parietal epithelial cell density, podocyte density, and glomerulosclerosis.
- Analysis of phosphorylated ERK 1/2 (pERK), alpha-smooth muscle actin (α-SMA), and phospho-S6 ribosomal protein (pS6RP) expression.
Main Results:
- Aged CD44-/- mice showed reduced pERK, vimentin, and α-SMA in PECs compared to aged CD44+/+ mice.
- Glomerular hypertrophy and glomerulosclerosis were significantly lower in aged CD44-/- mice.
- Podocyte density was higher, and mTOR activation (pS6RP) was lower in aged CD44-/- mice.
Conclusions:
- Increased CD44 in aged PECs contributes to glomerular changes during healthy aging.
- CD44 appears to mediate age-related kidney alterations possibly through ERK and mTOR pathways.
- Targeting CD44 may offer a therapeutic strategy for age-related kidney diseases.
Abstract:
CD44 contributes to the activation of glomerular parietal epithelial cells (PECs). Although CD44 expression is higher in PECs of healthy aged mice, the biological role of CD44 in PECs in this context remains unclear. Accordingly, young (4 months) and aged (24 months) CD44-/- mice were compared to age-matched CD44+/+ mice, both aged in a nonstressed environment. Parietal epithelial cell densities were similar in both young and aged CD44+/+ and CD44-/- mice. Phosphorylated ERK 1/2 (pERK) was higher in aged CD44+/+ mice. Vimentin and α-SMA, markers of changes to the epithelial cell phenotype, were present in PECs in aged CD44+/+ mice, but absent in aged CD44-/- mice in both outer cortical (OC) and juxtamedullary (JM) glomeruli. Because age-related glomerular hypertrophy was lower in CD44-/- mice, mTOR activation was assessed by phospho-S6 ribosomal protein (pS6RP) staining. Parietal epithelial cells and glomerular tuft staining for pS6RP was lower in aged CD44-/- mice compared to aged CD44+/+ mice. Podocyte density was higher in aged CD44-/- mice in both OC and JM glomeruli. These changes were accompanied by segmental and global glomerulosclerosis in aged CD44+/+ mice, but absent in aged CD44-/- mice. These results show that the increase in CD44 in PECs in aged kidneys contributes to several changes to the glomerulus during healthy aging in mice, and may involve ERK and mTOR activation.
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