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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...

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Autores principales: Hamatani, Hiroko, Eng, Diana G., Hiromura, Keiju, Pippin, Jeffrey W., Shankland, Stuart J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322268/
https://www.ncbi.nlm.nih.gov/pubmed/32597007
http://dx.doi.org/10.14814/phy2.14487
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author Hamatani, Hiroko
Eng, Diana G.
Hiromura, Keiju
Pippin, Jeffrey W.
Shankland, Stuart J.
author_facet Hamatani, Hiroko
Eng, Diana G.
Hiromura, Keiju
Pippin, Jeffrey W.
Shankland, Stuart J.
author_sort Hamatani, Hiroko
collection PubMed
description 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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spelling pubmed-73222682020-06-30 CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney Hamatani, Hiroko Eng, Diana G. Hiromura, Keiju Pippin, Jeffrey W. Shankland, Stuart J. Physiol Rep Original Research 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. John Wiley and Sons Inc. 2020-06-29 /pmc/articles/PMC7322268/ /pubmed/32597007 http://dx.doi.org/10.14814/phy2.14487 Text en © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Hamatani, Hiroko
Eng, Diana G.
Hiromura, Keiju
Pippin, Jeffrey W.
Shankland, Stuart J.
CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322268/
https://www.ncbi.nlm.nih.gov/pubmed/32597007
http://dx.doi.org/10.14814/phy2.14487
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