The Glomerulosclerosis of Aging in Females
The American Journal of Pathology. 2004-11-01; 165(5): 1789-1798
DOI: 10.1016/s0002-9440(10)63434-7
Lire sur PubMed
1. Am J Pathol. 2004 Nov;165(5):1789-98. doi: 10.1016/S0002-9440(10)63434-7.
The glomerulosclerosis of aging in females: contribution of the proinflammatory
mesangial cell phenotype to macrophage infiltration.
Zheng F(1), Cheng QL, Plati AR, Ye SQ, Berho M, Banerjee A, Potier M, Jaimes EA,
Yu H, Guan YF, Hao CM, Striker LJ, Striker GE.
Author information:
(1)Vascular Biology Institute, University of Miami School of Medicine,
Rosenstiel Medical Science Building, Room 1023A, 1600 NW 10th Ave., Miami, FL
33136, USA.
Age-associated renal changes may be an important cause of renal failure. We
recently found that aged female B6 mice developed progressive glomerular
lesions. This was associated with macrophage infiltration, a frequent finding in
glomerulosclerosis. We used these mice as a model for studying the mechanisms of
glomerular aging. We compared the gene expression profile of intact glomeruli
from late postmenopausal (28-month-old) mice to that of intact glomeruli from
premenopausal (5-month-old) mice. We found that inflammation-related genes,
especially those expressed by activated macrophages, were up-regulated in the
glomeruli of 28-month-old mice, a result correlating with the histological
observation of glomerular macrophage infiltration. The mechanism for macrophage
recruitment could have been stable phenotypic changes in mesangial cells because
we found that mesangial cells isolated from 28-month-old mice expressed higher
levels of RANTES and VCAM-1 than cells from 5-month-old mice. The elevated serum
tumor necrosis factor (TNF)-alpha levels present in aged mice may contribute to
increased RANTES and VCAM-1 expression in mesangial cells. Furthermore, cells
from 28-month-old mice were more sensitive to TNF-alpha-induced RANTES and
VCAM-1 up-regulation. The effect of TNF-alpha on RANTES expression was mediated
by TNF receptor 1. Interestingly, mesangial cells isolated from 28-month-old
mice had increased nuclear factor-kappaB transcriptional activity. Inhibition of
nuclear factor-kappaB activity decreased baseline as well as TNF-alpha-induced
RANTES and VCAM-1 expression in mesangial cells isolated from 28-month-old mice.
Thus, phenotypic changes in mesangial cells may predispose them to inflammatory
stimuli, such as TNF-alpha, which would contribute to glomerular macrophage
infiltration and inflammatory lesions in aging.
DOI: 10.1016/S0002-9440(10)63434-7
PMCID: PMC1618669
PMID: 15509547 [Indexed for MEDLINE]