Estradiol suppresses type I collagen synthesis in mesangial cells via activation of activator protein-1

Sharon Silbiger, Jun Lei, Joel Neugarten

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Background. Estradiol suppresses the synthesis of type I collagen by murine mesangial cells. However, neither the α1(I) nor the α2(I) collagen gene contains an estrogen-response element. Because estradiol modulates the transcription of several genes that lack an estrogen-response element but contain a regulatory activator protein-1 (AP-1) binding motif, we hypothesized that AP-1 may mediate estradiol-induced suppression of type I collagen synthesis. Methods. We measured type I collagen synthesis in murine mesangial cells exposed to estradiol, phorbol 12-myristate 13-acetate (an activator of AP-1), or curcumin (an inhibitor of AP-1). We also assessed the effects of estradiol on the steady-state level of c-fos and c-jun mRNA and on the binding of mesangial cell nuclear extracts to an AP-1 consensus binding site oligonucleotide. Results. Estradiol (10-10 M to 10-7 M) suppressed type I collagen synthesis by murine mesangial cells in a dose-dependent manner (10-7 M, 43.7 ± 8.2% of control values, P < 0.001). Phorbol 12- myristate 13-acetate (10 μM, four-hr exposure) also decreased type I collagen in the media. In contrast, curcumin (1 μM) increased type I collagen. Estradiol increased the steady-state level of c-fos mRNA twofold at 30 minutes, with a return to basal levels at one hour. This was associated with a greater than threefold increase in the binding of nuclear extracts from estradiol-treated mesangial cells to an AP-1 consensus binding site oligonucleotide. Estradiol-enhanced binding of nuclear extracts to the AP-1 oligonucleotide was reversed by cycloheximide. Conclusions. These data suggest that estradiol suppresses collagen I synthesis by murine mesangial cells via enhanced AP-1 activity.

Original languageEnglish (US)
Pages (from-to)1268-1276
Number of pages9
JournalKidney international
Volume55
Issue number4
DOIs
StatePublished - Jan 1 1999

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Keywords

  • Activator protein-1
  • Gentler hormones
  • Mesangial matrix
  • Progressive renal disease
  • Transcription factors

ASJC Scopus subject areas

  • Nephrology

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