EMMPRIN is secreted by human uterine epithelial cells in microvesicles and stimulates metalloproteinase production by human uterine fibroblast cells

A. G. Braundmeier, C. A. Dayger, P. Mehrotra, R. J. Belton, R. A. Nowak

Research output: Contribution to journalArticlepeer-review

Abstract

Endometrial remodeling is a physiological process involved in the gynecological disease, endometriosis. Tissue remodeling is directed by uterine fibroblast production of matrix metalloproteinases (MMPs). Several MMPs are regulated directly by the protein extracellular matrix metalloproteinase inducer (EMMPRIN) and also by proinflammatory cytokines such as interleukin (IL)1-α/β. We hypothesized that human uterine epithelial cells (HESs) secrete intact EMMPRIN to stimulate MMPs. Microvesicles from HES cell-conditioned medium (CM) expressed intact EMMPRIN protein. Treatment of HES cells with estradiol or phorbyl 12-myristate-13-acetate increased the release of EMMPRIN-containing microvesicles. The HES CM stimulated MMP-1, -2, and -3 messenger RNA levels in human uterine fibroblasts (HUFs) and EMMPRIN immunodepletion from HES-cell concentrated CM reduced MMP stimulation (P <.05). Treatment of HUF cells with low concentrations of IL-1β/α stimulated MMP production (P <.05). These results indicate that HES cells regulate MMP production by HUF cells by secretion of EMMPRIN, in response to ovarian hormones, proinflammatory cytokines as well as activation of protein kinase C.

Original languageEnglish (US)
Pages (from-to)1292-1301
Number of pages10
JournalReproductive Sciences
Volume19
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • EMMPRIN
  • MMPs
  • interleukin
  • microvesicles
  • uterus

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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