CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney

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 alpha-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.