title: Involvement of MAPKs in ICAM-1 expression in glomerular endothelial cells in diabetic nephropathy.
abstract: Inflammatory processes are involved in the pathogenesis of diabetic nephropathy. The aim of this study was to clarify the role of mitogen-activated protein kinase (MAPK) pathways for induction of intercellular adhesion molecule-1 (ICAM-1) expression in glomerular endothelial cells under diabetic conditions. We examined the expression of ICAM-1 in the kidneys of experimental diabetic rats. Human glomerular endothelial cells (GE cells) were exposed to normal glucose concentration, high glucose concentration (HG), or high mannitol concentration (HM), and then the expression of the ICAM-1 protein and the phosphorylation of the 3 subfamilies of mitogen-activated protein kinase (MAPK) were determined using Western blot analysis. Next, to evaluate the involvement of MAPKs in HG- or HM-induced ICAM-1 expression, we preincubated GE cells with the inhibitors for ERK, p38 or JNK 1h prior to the application of glucose or mannitol. Expression of ICAM-1 was increased in the glomeruli of diabetic rats. Both HG and HM induced ICAM-1 expression and phosphorylation of ERK1/2, p38 and JNK in GE cells. Expression of ICAM-1 was significantly attenuated by inhibitors of ERK, p38 and JNK. We conclude that activation of ERK1/2, p38 and JNK cascades may be involved in ICAM-1 expression in glomerular endothelial cells under diabetic conditions.
authors.affiliation: Departments of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Watanabe
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shikata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shikata
authors.forename: Kei
authors.initials: K
authors.lastname: Sarai
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Omori
authors.forename: Ryo
authors.initials: R
authors.lastname: Kodera
authors.forename: Chikage
authors.initials: C
authors.lastname: Sato
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018799:Intercellular Adhesion Molecule-1; D008353:Mannitol; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose