Prostaglandin F2α facilitates collagen synthesis in cardiac fibroblasts via an F-prostanoid receptor/protein kinase C/Rho kinase pathway independent of transforming growth factor β1

Abstract

Accumulation of collagen I and III in the myocardium is a prominent feature of interstitial fibrosis. Prostaglandin F2α (PGF2α) facilitates fibrosis by increasing collagen synthesis. However, the underlying mechanisms mediating the effect of PGF2α on collagen expression in cardiac fibroblasts are not yet fully elucidated. We measured the mRNA and protein levels of collagen I and III by quantitative real-time PCR and ELISA, respectively. Activation of signaling pathways was determined by western blot analysis. In primary rat cardiac fibroblasts, treatment with PGF2α stimulated both the mRNA and protein levels of collagen I and III, and pretreatment with the F-prostanoid (FP) receptor antagonist AL-8810, protein kinase C inhibitor LY-333531, and Rho kinase inhibitor Y-27632 significantly inhibited PGF2α-induced collagen I and III expression. FP receptor, protein kinase C, and Rho kinase were activated with PGF2α treatment. PGF2α may be an important regulator in the synthesis of collagen I and III via an FP receptor/protein kinase C/Rho kinase cascade in cardiac fibroblasts, which might be a new therapeutic target for myocardial fibrosis.