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Publication : Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors.

First Author  Feng Z Year  2005
Journal  Am J Pathol Volume  167
Issue  2 Pages  355-63
PubMed ID  16049323 Mgi Jnum  J:99952
Mgi Id  MGI:3584293 Doi  10.1016/S0002-9440(10)62981-1
Citation  Feng Z, et al. (2005) Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors. Am J Pathol 167(2):355-63
abstractText  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.
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