17 Β-estradiol and tamoxifen upregulate estrogen receptor Β expression and control podocyte signaling pathways in a model of type 2 diabetes

Paola Catanuto, Sophie Doublier, Enrico Lupia, Alessia Fornoni, Mariana Berho, Michael Karl, Gary E. Striker, Xiaomei Xia, Sharon Elliot

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racialethnic minorities. Although administration of 17Β-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated dbdb mice, a model of type 2 diabetic glomerulosclerosis, with 17Β-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17Β-estradiol treatment decreased podocyte transforming growth factor-Β mRNA expression but increased that of the estrogen receptor subtype Β protein. 17Β-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17Β-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)1194-1201
Number of pages8
JournalKidney international
Volume75
Issue number11
DOIs
StatePublished - Jun 1 2009

Keywords

  • Diabetic glomerulosclerosis
  • Estrogen
  • Podocytes

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of '17 Β-estradiol and tamoxifen upregulate estrogen receptor Β expression and control podocyte signaling pathways in a model of type 2 diabetes'. Together they form a unique fingerprint.

  • Cite this