岡山医学会 Acta Medica Okayama 0030-1558 123 3 2011 P-selectin glycoprotein ligand-1 (PSGL-1) 抑制による肥満におけるインスリン抵抗性の改善効果 177 183 EN Chikage Sato No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 4 2011 Involvement of MAPKs in ICAM-1 Expression in Glomerular Endothelial Cells in Diabetic Nephropathy 247 257 EN Naomi Watanabe Kenichi Shikata Yasushi Shikata Kei Sarai Kazuyoshi Omori Ryo Kodera Chikage Sato Jun Wada Hirofumi Makino Original Article 10.18926/AMO/46850 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 2 2011 The Macrophage Is a Key Factor in Renal Injuries Caused by Glomerular Hyperfiltration 81 89 EN Motofumi Sasaki Kenichi Shikata Shinichi Okada Satoshi Miyamoto Shingo Nishishita Hitomi Usui Kataoka Chikage Sato Jun Wada Daisuke Ogawa Hirofumi Makino Original Article 10.18926/AMO/45266 Glomerular hyperfiltration is a common pathway leading to glomerulosclerosis in various kinds of kidney diseases. The 5/6 renal ablation is an established experimental animal model for glomerular hyperfiltration. On the other hand, low-grade inflammation is also a common mechanism for the progression of kidney diseases including diabetic nephropathy and atherosclerosis. Here we analyzed the gene expression profile in the remnant kidney tissues of 5/6 nephrectomized mice using a DNA microarray system and compared it with that of sham-operated control mice. The 5/6 nephrectomized mice showed glomerular hypertrophy and an increase in the extracellular matrix in the glomeruli. DNA microarray analysis indicated the up-regulated expression of various kinds of genes related to the inflammatory process in remnant kidneys. We confirmed the up-regulated expression of platelet factor-4, and monocyte chemoattractant protein-1, 2, and 5 in remnant kidneys by RT-PCR. The current results suggest that the inflammatory process is involved in the progression of glomerulosclerosis and is a common pathway of the pathogenesis of kidney disease. No potential conflict of interest relevant to this article was reported.