Estrogen-Related Abnormalities in Glomerulosclerosis-Prone Mice
The American Journal of Pathology. 2002-05-01; 160(5): 1877-1885
DOI: 10.1016/s0002-9440(10)61134-0
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1. Am J Pathol. 2002 May;160(5):1877-85. doi: 10.1016/S0002-9440(10)61134-0.
Estrogen-related abnormalities in glomerulosclerosis-prone mice: reduced
mesangial cell estrogen receptor expression and prosclerotic response to
estrogens.
Potier M(1), Karl M, Zheng F, Elliot SJ, Striker GE, Striker LJ.
Author information:
(1)Vascular Biology Institute, Department of Medicine, University of Miami
School of Medicine, Miami, Florida 33101, USA.
The development and progression of glomerulosclerosis (GS) is determined by the
genetic background. The incidence of end-stage renal disease is increased in
postmenopausal women, suggesting that estrogen deficiency may play a role in the
accumulation of extracellular matrix by mesangial cells (MCs), which are
primarily responsible for the synthesis and degradation of this matrix. Using
mouse models that are prone or resistant to the development of GS, we compared
the expression of estrogen receptor (ER)-alpha and ER-beta subtypes in GS-prone
and GS-resistant glomeruli and isolated MCs, and examined the effects of
estrogens on ER, collagen, and matrix metalloproteinase (MMP) expression in MCs.
Glomeruli and MCs from GS-prone mice had decreased expression of ER-alpha and
ER-beta subtypes and ER transcriptional activity was also decreased in their
MCs. Importantly, although 17 beta-estradiol treatment resulted in decreased
collagen accumulation and increased MMP-9 expression and activity in MCs from
GS-resistant mice, there was, paradoxically, no effect on collagen accumulation
and decreased MMP-9 expression and activity in MCs from GS-prone mice. Thus, GS
susceptibility is associated with diminished ER expression in MCs. The renal
protective effects of estrogens, including decreased collagen accumulation and
increased MMP-9 expression, seem to be blunted in GS-prone MCs.
DOI: 10.1016/S0002-9440(10)61134-0
PMCID: PMC1850880
PMID: 12000739 [Indexed for MEDLINE]