Role Of The Prostaglandin E2/E-Prostanoid 2 Receptor Signalling Pathway In Tgf Beta-Induced Mice Mesangial Cell Damage

The prostaglandin E2 receptor, EP2 (E-prostanoid 2), plays an important role in mice glomerular MCs (mesangial cells) damage induced by TGF beta 1 (transforming growth factor-beta 1); however, the molecular mechanisms for this remain unknown. The present study examined the role of the EP2 signalling pathway in TGF beta 1-induced MCs proliferation, ECM (extracellular matrix) accumulation and expression of PGES (prostaglandin E-2 synthase). We generated primary mice MCs. Results showed MCs proliferation promoted by TGF beta 1 were increased; however, the production of cAMP and PGE(2) (prostaglandin E-2) was decreased. EP2 deficiency in these MCs augmented FN (fibronectin), Col I (collagen type I), COX2 (cyclooxygenase-2), mPGES-1 (membrane-associated prostaglandin E1), CTGF (connective tissue growth factor) and CyclinD1 expression stimulated by TGF beta 1. Silencing of EP2 also strengthened TGF beta 1-induced p38MAPK (mitogen-activated protein kinase), ERK1/2 (extracellular-signal-regulated kinase 1/2) and CREB1 (cAMP responsive element-binding protein 1) phosphorylation. In contrast, Adenovirus-mediated EP2 overexpression reversed the effects of EP2-siRNA (small interfering RNA). Collectively, the investigation indicates that EP2 may block p38MAPK, ERK1/2 and CREB1 phosphorylation via activation of cAMP production and stimulation of PGE2 through EP2 receptors which prevent TGF beta 1-induced MCs damage. Our findings also suggest that pharmacological targeting of EP2 receptors may provide new inroads to antagonize the damage induced by TGF beta 1.