Calcium Signal Pathway is Involved in Prostaglandin E2 Induced Cardiac Fibrosis in Cardiac Fibroblasts

Prostaglandin E-2 (PGE(2)), one of the arachidonic acid metabolites synthetized from arachidonic acid through cyclooxygenase (COX) catalysis, demonstrates multiple physiological and pathological actions through different subtypes of EP receptors. Purpose: The present study was designed to explore the effects of PGE(2) on cardiac fibrosis and the involved mechanism. Methods: We used Western blot analysis, real-time quantitative PCR and immunostaining to assess the mechanism. Results: Our data showed that in cultured adult rat cardiac fibroblasts (CFs), PGE(2) effectively promoted the expression of alpha-smooth muscle actin (alpha-SMA), connective tissue growth factor (CTGF), fibronectin (FN) and collagen I, and induced [Ca2+](i) increase. Besides, calcium increase evoked by PGE(2) is mediated by virtue of EP1 activation. Instead of EP3 or EP4, inhibition of EP1 attenuated PGE(2)-stimulated upregulation of alpha-SMA, CTGF, FN, collagen I and [Ca2+](i), as well as the nuclear factor of activated T cell cytoplasmic 4 protein (NFATc4) translocation. Conclusions: PGE(2) appears to promote cardiac fibrosis via EP1 receptor and calcium signal pathway.