Glomerular Aging in Females Is a Multi-Stage Reversible Process Mediated by Phenotypic Changes in Progenitors
The American Journal of Pathology. 2005-08-01; 167(2): 355-363
DOI: 10.1016/s0002-9440(10)62981-1
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1. Am J Pathol. 2005 Aug;167(2):355-63. doi: 10.1016/S0002-9440(10)62981-1.
Glomerular aging in females is a multi-stage reversible process mediated by
phenotypic changes in progenitors.
Feng Z(1), Plati AR, Cheng QL, Berho M, Banerjee A, Potier M, Jy WC, Koff A,
Striker LJ, Striker GE.
Author information:
(1)Department of Medicine, Division of Nephrology, Vascular Biology Institute,
University of Miami School of Medicine, Florida, USA.
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.
DOI: 10.1016/S0002-9440(10)62981-1
PMCID: PMC1603557
PMID: 16049323 [Indexed for MEDLINE]