title: Methylglyoxal induces prostaglandin E2 production in rat mesangial cells.
abstract: The formation of methylglyoxal (MG), a reactive dicarbonyl compound, is accelerated under hyperglycemia, presumably contributing to tissue injury in diabetes. On the other hand, prostaglandin E2 (PGE2) has been implicated in glomerular hyperfiltration, a characteristic change in the early stage of diabetic nephropathy. We therefore examined whether MG was capable of inducing PGE2 production in rat mesangial cells (RMC) to address a possible mechanism by which hyperglycemia-derived dicarbonyls accelerated the development of diabetic nephropathy. RMC were incubated with 0 - 200 microM of MG, followed by determination of secreted PGE2 by enzyme immunoassay (EIA). We further investigated the intracellular mechanisms mediating the MG-induced PGE2 synthesis, focusing particularly on cyclooxygenase-2 (COX-2) and the MAPK superfamily. Our results indicated that MG induced PGE2 production in a dose-dependent manner, accompanied by augmentation of COX-2 mRNA expression. This MG-induced PGE2 production was significantly suppressed by inhibiting either ERK1/2 or p38 MAPK, implicating involvement of the MAPK superfamily. Our results suggest a potential role of MG in the development of diabetic nephropathy through PGE2 production, and may serve as a novel insight into the therapeutic strategies for diabetic nephropathy.
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Uriuhara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyata
authors.forename: Bing-Fen
authors.initials: BF
authors.lastname: Liu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kusunoki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga