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PGE2 reduces MMP expression and cell migration in neonatal ventricular fibroblasts
Author(s) -
He Quan,
LaPointe Margot C,
Harding Pamela
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1031.6
Subject(s) - prostaglandin e2 receptor , matrix metalloproteinase , agonist , receptor , prostaglandin e2 , chemistry , cell migration , medicine , activator (genetics) , extracellular matrix , endocrinology , fibroblast , extracellular , prostaglandin , microbiology and biotechnology , cell , biology , in vitro , biochemistry
Prostaglandin E2 (PGE2) is elevated during cardiac remodeling and we have shown that mice lacking the PGE2 EP4 receptor subtype develop dilated cardiomyopathy (DCM) with increased expression of matrix metalloproteinases (MMP) 14 and 23. Fibroblasts are the major contributor to DCM by altering the extracellular matrix network. Cardiac fibroblasts express all four PGE2 EP receptors (EP1‐EP4). We hypothesized that PGE2 regulates expression of MMPs and affects fibroblast migration. We used primary cultures of neonatal rat ventricular fibroblasts (NVFs) to test the effects of PGE2. Expression of genes was assessed by real time RT‐PCR while migration of NVF was determined by motility in a transwell system. PGE2 (1 μM) reduced expression of MMP‐14 and MMP‐23 by 53% and 54%, respectively (p < 0.01). The reductions were blunted by 10 μM ONO AE3‐208, an EP4 antagonist. PGE2 also increased expression of plasminogen activator inhibitor‐1, an inhibitor of MMP activation, from 1.00 to 6.02 (arbitrary units). This was also prevented by EP4 inhibition. Treatment of NVFs with PGE2 for 4 hours reduced the number of migrating cells from 156 ± 11 to 116 ± 9 (p < 0.05). Five μM Butaprost, an agonist acting on the EP2 sub‐type, also reduced migration from 168 ± 8 to 119 ± 7 (p < 0.005). In contrast, EP4 agonist had no effect on NVF migration. These results suggest that PGE2 decreases MMP expression and/or activation via EP4 and NVF migration via EP2.