Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts

Abstract

An increasing number of studies have shown that prostaglandins (PGs) exert multiple regulatory actions in the processes associated to tissue remodeling and fibrosis. Extracellular matrix (ECM) turnover is mediated by matrix metallopeptidases (MMPs). The knowledge about the regulation of their expression in mare endometrium is still limited. Thus, the aim of this study was to investigate whether: (i) profibrotic transforming growth factor (TGF)-β1 modulates PG production in equine endometrium; and (ii) PGE₂ and PGF_2α modulate MMPs, their tissue inhibitors (TIMPs), and collagen 1 (COL1) expression. In experiment 1, the effect of TGF-β1 (5 ng/mL) on PG secretion and PG synthases mRNA transcription, after 24 and 48 h treatment of mare endometrial fibroblast and epithelial cells was investigated using ELISA and qPCR. In experiment 2, the effects of PGE₂ and PGF_2α in doses 10_^-7M and 10^-8M on secretion and MMP1, 2, 9, 13, TIMP1, 2, and COL1A1 mRNA transcription in mare endometrial fibroblasts were assessed. Transforming growth factor-β1 treatment decreased secretion of PGF_2α by endometrial fibroblasts (P < 0.05) and PGF_2α and PGE₂ by endometrial epithelial cells (P < 0.05). Prostaglandin E₂ increased MMP-2 and MMP-9, and decreased MMP-13 secretion by endometrial fibroblasts (P < 0.05). Additionally, PGF_2α treatment increased MMP-2, MMP-13 and COL1, but decreased MMP-1 secretion by endometrial fibroblasts (P < 0.05). Prostaglandins may be involved in the processes associated to pathological endometrial remodeling by their effect on MMP expression. The effect of PGF_2α on COL1 secretion from fibroblasts suggests its profibrotic role in pathological endometrial remodeling.