CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney
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 compa...
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Online Access: | https://doi.org/10.14814/phy2.14487 |
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doaj-3a509e881bd24b8da30aae102381ef9f2020-11-25T03:22:20ZengWileyPhysiological Reports2051-817X2020-06-01812n/an/a10.14814/phy2.14487CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidneyHiroko Hamatani0Diana G. Eng1Keiju Hiromura2Jeffrey W. Pippin3Stuart J. Shankland4Division of Nephrology University of Washington School of Medicine Seattle WA USADivision of Nephrology University of Washington School of Medicine Seattle WA USADepartment of Nephrology and Rheumatology Gunma University Graduate School of Medicine Maebashi JapanDivision of Nephrology University of Washington School of Medicine Seattle WA USADivision of Nephrology University of Washington School of Medicine Seattle WA USAAbstract 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.https://doi.org/10.14814/phy2.14487Bowman's capsulecorticalmedullarymTORpERKpodocyte |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiroko Hamatani Diana G. Eng Keiju Hiromura Jeffrey W. Pippin Stuart J. Shankland |
spellingShingle |
Hiroko Hamatani Diana G. Eng Keiju Hiromura Jeffrey W. Pippin Stuart J. Shankland CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney Physiological Reports Bowman's capsule cortical medullary mTOR pERK podocyte |
author_facet |
Hiroko Hamatani Diana G. Eng Keiju Hiromura Jeffrey W. Pippin Stuart J. Shankland |
author_sort |
Hiroko Hamatani |
title |
CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney |
title_short |
CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney |
title_full |
CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney |
title_fullStr |
CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney |
title_full_unstemmed |
CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney |
title_sort |
cd44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney |
publisher |
Wiley |
series |
Physiological Reports |
issn |
2051-817X |
publishDate |
2020-06-01 |
description |
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. |
topic |
Bowman's capsule cortical medullary mTOR pERK podocyte |
url |
https://doi.org/10.14814/phy2.14487 |
work_keys_str_mv |
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