Expression and regulation of estrogen receptors in mesangial cells: Influence on matrix metalloproteinase-9

M. Potier, S. J. Elliot, I. Tack, O. Lenz, G. E. Striker, L. J. Striker, M. Karl

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Diabetic glomerulosclerosis is characterized by the accumulation of extracellular matrix (ECM) in the mesangium. Estrogens seem to retard whereas estrogen deficiency seems to accelerate progressive glomerulosclerosis. Thus, mesangial cells (MC) may be a target for estrogens. Estrogen action is mediated via estrogen receptor (ER) subtypes ERα and ERβ. Both ER subtypes were expressed in human and mouse MC. Using an estrogen-responsive reporter construct in transfection assays, it also was demonstrated that the nuclear ER were transcriptionally active. In the presence of 17β-estradiol (E2; 10-10 to 10-8 M), there was a progressive increase in the mRNA levels of both ERα (approximately 1.8-fold and approximately 2.7-fold after 24 and 72 h, respectively) and ERβ (approximately 1.3-fold and approximately 2.2-fold after 24 and 72 h, respectively). ERα protein levels increased approximately 2.5-fold after 24 h (10-10 M, E2) and up to approximately 5.4-fold after 72 h (10-9 M, E2). ERβ protein levels increased approximately 2.1-fold in the presence of E2 (10-9 M) after 24 h. Thus, estrogens positively regulate the expression of the ER subtypes, thereby maintaining or increasing MC responsiveness to estrogens. Because diabetic glomemlosclerosis may be due partly to a decrease in ECM degradation, the effects of estrogens on matrix metalloproteinases (MMP) were studied. It was found that E2 (10-10 to 10-8 M) increased both MMP-9 mRNA and MMP-9 activity in MC. This may be an important mechanism by which estrogens influence ECM turnover and protect against progression of diabetic glomemlosclerosis.

Original languageEnglish (US)
Pages (from-to)241-251
Number of pages11
JournalJournal of the American Society of Nephrology
Volume12
Issue number2
StatePublished - 2001

ASJC Scopus subject areas

  • Nephrology

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