title: Role of the prostaglandin E2 receptor agonists in TGF-β1-induced mesangial cell damage.
abstract: PGE2exerts its biological effect through binding to various EP receptors that result inactivation of various signal transduction pathways. It also plays an important role in mice glomerular mesangial cells (MCs) damage induced by transforming growth factor-β1 (TGF-β1); however, the molecular mechanisms remain unknown. In the present study, we tested the efficacy of four selective agonists of PGE2receptor, EP1A (17-phenyl trinor prostaglandin E2ethyl amid), EP2A (butaprost), EP3A (sulprostone) and EP4A (cay10580), on mice MCs. Compared with the cAMP produced by TGF-β1, additional pretreatment of EP3A decreased the cAMP level. MCs treated with EP1A and EP3A augmented PGE2, cyclooxygenase-2 (COX-2), membrane-bound PGE synthase 1 (mPGES1), laminin (LN), connective tissue growth factor (CTGF) and cyclin D1 expression stimulated by TGFβ1. EP1A and EP3A increased the number of cells in S+G2/M phase and reduced cells in G0/G1 phase. EP1and EP3agonists also strengthened TGFβ1-induced mitogen-activated protein kinase (p38MAPK) and extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Whereas MCs treated with EP2A and EP4A weakened PGE2, COX-2, mPGES1, LN, CTGF and cyclin D1 expression stimulated by TGFβ1. EP2A and EP4A decreased the number of cells in S+G2/M phase and increased cells in G0/G1 phase. EP2and EP4agonists weakened TGFβ1-induced p38MAPK and ERK1/2 phosphorylation. These findings suggest that PGE2has an important role in the progression of kidney disease via the EP1/EP3receptor, whereas EP2and EP4receptors are equally important in preserving the progression of chronic kidney failure. Thus, agonists of EP2and EP4receptors may provide a basis for treating kidney damage induced by TGF-β1.
authors: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China Department of Emergency, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Pei-Pei
authors: PP
authors: Xi
authors: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Yu-Yin
authors: YY
authors: Xu
authors: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China chenxl8448@sina.com.
authors: Xiao-Lan
authors: XL
authors: Chen
authors: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Ya-Ping
authors: YP
authors: Fan
authors: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Jian-Hua
authors: JH
authors: Wu
keywords: MAPKs signalling pathway; TGF-β1; agonist; mesangial cells; prostaglandin E2 receptors