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Proinsulin C-peptide induces c-Jun N-terminal kinase 1 expression in LEII mouse lung capillary endothelial cells
2009
Furuya, D.T., Hokkaido Univ., Sapporo (Japan) | Ishii, T. | Kamikawa, A. | Shimada, K. | Machado, U.F. | Saito, M.;Kimura | Kimura, K.
To characterize the roles of C-peptide in vascular homeostatic processes, we examined the genes regulated by C-peptide in LEII mouse lung microvascular endothelial cells. Treatment of the cells with C-peptide increased the expression of c-Jun N-terminal kinase 1 (JNK1) mRNA dose-dependently, accompanied by an increase in JNK1 protein content. Prior treatment of the cells with PD98059, an ERK kinase inhibitor or SB203580, a p38MAPK inhibitor, abrogated the C-peptide-elicited JNK1 mRNA expression. These results indicate that C-peptide increases JNK1 protein levels, possibly through ERK- and p38MAPK-dependent activation of JNK gene transcription.
Show more [+] Less [-]Upregulation of renal renin-angiotensin system in mouse diabetic nephropathy
2005
Tamura, J.(Hokkaido Univ., Sapporo (Japan)) | Konno, A. | Hashimoto, Y. | Kon, Y.
The aim of this study was to clarify the role of the renal renin-angiotensin system (RAS) in diabetic nephropathy (DN) , which was induced by injection of streptozotocin (STZ). Male CBA/N and CBA/J mice were compared in this study. The former possesses a single renin gene, Ren1. whereas the latter carries two renin genes, Ren1 and Ren2. To examine the molecular dynamics of renal RAS, including renin, angiotensinogen (Agt), angiotensin-converting enzyme (Ace), angiotensin type 1 (Agtr1) and type 2 (Agtr2) receptors in experimental DN, we performed laser-microdissection (LMD) followed by reverse transcriptase nested polymerase chain reaction using each specific primer pairs and immunohistochemistry for renin and angiotensin 2. CBA/N mice had a higher response after injection of STZ than CBA/J mice, showing a significant increase of the kidney/body weight ratio, although there was no significant difference between the two strains for the blood glucose level or pancreatic beta-cell response. The onset of renal pathological changes associated with DN was earlier and more severe in CBA/N mice than in CBA/J mice. Distinct immunoreactivities for renin and angiotensin 2 were newly distributed on the flattered epithelial cells in the dilated distal tubules in the cortex as well as the collecting ducts in the cortex and medulla, and were demonstrated more intensity in CBA/N mice than in CBA/J mice. Micro dissectional analysis in both models revealed a higher incidence of RAS-related gene expression in CBA/J, Ren 2 mice than in CBA-N, Ren 1 mice.
Show more [+] Less [-]Chronic cadmium treatment induces islet B cell injury in ovariectomized cynomolgus monkeys
2003
Kurata, Y. (Hokkaido Univ., Sapporo (Japan)) | Katsuta, O. | Doi, T. | Kawasuso, T. | Hiratsuka, H. | Tsuchitani, M. | Umemura, T.