Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors Journal Article


Authors: Feng, Z.; Plati, A. R.; Cheng, Q. L.; Berho, M.; Banerjee, A.; Potier, M.; Jy, W. C.; Koff, A.; Striker, L. J.; Striker, G. E.
Article Title: Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors
Abstract: The glomeruli of postmenopausal C57BL6 mice, and age-matched, males, show progressive hypertrophy and glomerulosclerosis. We asked whether this was a multistage process, was due to alterations in glomerular progenitors, and was reversible in female mice. Using cross bone marrow transplants (BMT) between young and old females, we found that BMT delivered a phenotype that was donor age-specific. The fact that lesions in young recipients were more severe if the donors were in late rather than early menopause suggested that new progenitor phenotypes had appeared. Postmenopausal recipients of BMT from young donors had reduced glomerular hypertrophy and sclerosis, implying that the aging lesions in females were reversible and that progenitors, rather than the local environment, determined the glomerular profile. The altered phenotype included increased extracellular matrix synthesis and decreased matrix metalloproteinase-2 levels as well as cell hypertrophy. The mechanism of the cellular hypertrophy was due to uncoupling of hypertrophy from proliferation, resulting from elevated p27 levels. Thus, glomerular hypertrophy and sclerosis in aging females is a multistage process, is reversible, and may be determined by the phenotype of bone marrow-derived progenitor cells. Copyright © American Society for Investigative Pathology.
Keywords: controlled study; nonhuman; flow cytometry; cell proliferation; cell cycle protein; animal cell; mouse; phenotype; animal; cytology; metabolism; animals; cell cycle proteins; mice; animal tissue; animal experiment; animal model; mice, inbred c57bl; physiology; c57bl mouse; stem cell; extracellular matrix; enzyme immunoassay; immunoenzyme techniques; blotting, western; cyclin dependent kinase inhibitor 1b; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; western blotting; stem cells; aging; age distribution; cdkn1a protein, mouse; cyclin dependent kinase inhibitor 1a; cyclin-dependent kinase inhibitor p21; menopause; bone marrow transplantation; tumor suppressor protein; postmenopause; cell aging; sclerosis; gelatinase a; cdkn1b protein, mouse; disease activity; hypertrophy; kidney glomerulus; matrix metalloproteinase 2; glomerulus; glomerulosclerosis; mesangium; glomerular mesangium
Journal Title: American Journal of Pathology
Volume: 167
Issue: 2
ISSN: 0002-9440
Publisher: Elsevier Science, Inc.  
Date Published: 2005-08-01
Start Page: 355
End Page: 363
Language: English
PUBMED: 16049323
PROVIDER: scopus
PMCID: PMC1603557
DOI: 10.1016/S0002-9440(10)62981-1
DOI/URL:
Notes: --- - "Cited By (since 1996): 17" - "Export Date: 24 October 2012" - "CODEN: AJPAA" - "Source: Scopus"
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  1. Andrew C Koff
    98 Koff