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

Autor:	Diana G. Eng, Stuart J. Shankland, Keiju Hiromura, Hiroko Hamatani, Jeffrey W. Pippin
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	MAPK/ERK pathway Male medicine.medical_specialty Bowman's capsule podocyte Physiology Kidney Glomerulus Context (language use) Vimentin cortical Ageing and Degeneration 030204 cardiovascular system & hematology Kidney lcsh:Physiology Podocyte 03 medical and health sciences Mice 0302 clinical medicine pERK Physiology (medical) Internal medicine medicine Animals Phosphorylation PI3K/AKT/mTOR pathway medullary Original Research Mice Knockout Mitogen-Activated Protein Kinase 3 biology lcsh:QP1-981 Chemistry Podocytes TOR Serine-Threonine Kinases CD44 Age Factors Epithelial Cells Glomerular Hypertrophy Disease Models Animal medicine.anatomical_structure Endocrinology Hyaluronan Receptors biology.protein mTOR Female Kidney Diseases Cellular Physiology 030217 neurology & neurosurgery
Zdroj:	Physiological Reports Physiological Reports, Vol 8, Iss 12, Pp n/a-n/a (2020)
ISSN:	2051-817X
Popis:	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. The absence of CD44 in aged null mice was accompanied by reduced glomerulosclerosis, glomerular hypertrophy, mTOR activation, and PEC activation, supporting a probable role for CD44 in kidney aging.
Databáze:	OpenAIRE
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