Methylglyoxal Induces Prostaglandin E2 Production in Rat Mesangial Cells

概要

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The formation of methylglyoxal (MG), a reactive dicarbonyl compound, isaccelerated under hyperglycemia, presumably contributing to tissue injury in diabetes.On the other hand, prostaglandin E2 (PGE2) has been implicated in glomerularhyperfiltration, a characteristic change in the early stage of diabetic nephropathy. Wetherefore examined whether MG was capable of inducing PGE2 production in ratmesangial cells (RMC) to address a possible mechanism by whichhyperglycemia-derived dicarbonyls accelerated the development of diabeticnephropathy. RMC were incubated with 0 - 200 μM of MG, followed by determinationof secreted PGE2 by enzyme immunoassay (EIA). We further investigated theintracellular mechanisms mediating the MG-induced PGE2 synthesis, focusingparticularly on cyclooxygenase-2 (COX-2) and the MAPK superfamily. Our resultsindicated that MG induced PGE2 production in a dose-dependent manner,accompanied by augmentation of COX-2 mRNA expression. This MG-induced PGE2production was significantly suppressed by inhibiting either ERK1/2 or p38 MAPK,implicating involvement of the MAPK superfamily. Our results suggest a potential roleof MG in the development of diabetic nephropathy through PGE2 production, and mayserve as a novel insight into the therapeutic strategies for diabetic nephropathy.