title: Expression and regulation of estrogen receptors in mesangial cells: influence on matrix metalloproteinase-9.
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 ERalpha and ERbeta. 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 17beta-estradiol (E2; 10(-10) to 10(-8) M), there was a progressive increase in the mRNA levels of both ERalpha (approximately 1.8-fold and approximately 2.7-fold after 24 and 72 h, respectively) and ERbeta (approximately 1.3-fold and approximately 2.2-fold after 24 and 72 h, respectively). ERalpha 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). ERbeta protein levels increased approximately 2.1-fold in the presence of E(2) (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 glomerulosclerosis 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 glomerulosclerosis.
authors.affiliation: Renal Cell Biology Laboratory, Division of Nephrology, University of Miami School of Medicine, Miami, Florida.
authors.forename: Mylene
authors.initials: M
authors.lastname: Potier
authors.affiliation: Renal Cell Biology Laboratory, Division of Nephrology, University of Miami School of Medicine, Miami, Florida.|Division of Endocrinology, Diabetes and Metabolism, University of Miami School of Medicine, Miami, Florida.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Elliot
authors.affiliation: Renal Cell Biology Laboratory, Division of Nephrology, University of Miami School of Medicine, Miami, Florida.
authors.forename: Ivan
authors.initials: I
authors.lastname: Tack
authors.affiliation: Renal Cell Biology Laboratory, Division of Nephrology, University of Miami School of Medicine, Miami, Florida.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Renal Cell Biology Laboratory, Division of Nephrology, University of Miami School of Medicine, Miami, Florida.|Division of Endocrinology, Diabetes and Metabolism, University of Miami School of Medicine, Miami, Florida.|Vascular Biology Institute, University of Miami School of Medicine, Miami, Florida.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Striker
authors.affiliation: Renal Cell Biology Laboratory, Division of Nephrology, University of Miami School of Medicine, Miami, Florida.|Vascular Biology Institute, University of Miami School of Medicine, Miami, Florida.
authors.forename: Liliane J
authors.initials: LJ
authors.lastname: Striker
authors.affiliation: Renal Cell Biology Laboratory, Division of Nephrology, University of Miami School of Medicine, Miami, Florida.|Division of Endocrinology, Diabetes and Metabolism, University of Miami School of Medicine, Miami, Florida.|Vascular Biology Institute, University of Miami School of Medicine, Miami, Florida.
authors.forename: Michael
authors.initials: M
authors.lastname: Karl
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011960:Receptors, Estrogen / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D020780:Matrix Metalloproteinase 9