Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH
2) to prostaglandin E2 (PGE
2), plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown.
[...] Read more.
Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH
2) to prostaglandin E2 (PGE
2), plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1
−/−) mice exhibited more severe fibrotic lesions with a decrease in PGE
2 content in lungs after bleomycin treatment when compared with wild type (mPGES-1
+/+) mice. The mPGES-1 expression levels and PGE
2 content were also decreased in bleomycin-treated mPGES-1
+/+ mice compared to saline-treated mPGES-1
+/+ mice. Moreover, in both mPGES-1
−/− and mPGES-1
+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2) and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5), siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-β1 (TGF-β1)-induced α-smooth muscle actin (α-SMA) protein expression, and the increase was reversed by treatment of PGE
2, selective EP2 agonist and focal adhesion kinase (FAK) inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE
2-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients.
Full article