An impact of HSP genes as new therapeutic target moleculesf or diabetic neplunpathy

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: ARAKI Shin-ichi Shiga University of Medical Science, Faculty of Medicine, Assistant Professor (80378455)
• Project Period (FY): 2005 – 2007
• Keywords: Diabetes / Diabetic Npehropathy / gene

Research Abstract

To explore new therapeutic target molecules which involve in the development of diabetic nephropathy, we created a time course data of gene expression profiles in the diabetic kidney by a DNA microarray method. Gene expression of the genes which belonged to Heat Shock Protein (HSP), stress responsiveness chaperonin, was inhibited in the kidney of the type 2 diabetic model mice, db/db mice, in comparison to the control mice, db/m nice, over the time-course. The protein levels of HSP70 were increased in the kidney from db/db mice only at the early course of diabetes and were then decreased. In cultured mesengial cells, high glucose medium induced the HSP70 expression, whereas oxidative stress inhibited the mRNA levels and protein levels of HSP70. In the mesangial cells which were constitutively over-expressed HSP70, oxidative stress-induced apoptosis was prevented. Erythropoietin which has a reno-protective effect was induced HSP70 expression in the renal cells and the kidney. These results suggest that, in the kidney of type 2 diabetic model mice, HSP70 expression first increases in response to hyperglycemia and then decreases due to oxidative stress enhanced by chronic diabetic condition. Thus, the failure of the anti-oxidative stress defense mechanism of HSP70 may involve in the development of diabetic nephropathy and an induction of HSP70 might be a tool to prevent diabetic nephropathy

Research Products

• [Journal Article] Asialoerythropoietin prevents contrast-induced nephropathy. (2008)
  • Author(s): Yokomaku Y, et. al.
  • Journal Title: J Am Soc Nephrol 19 Pages: 321-328
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Asialoerythropoietin prevents contrast-induced nephropathy (2008)
  • Author(s): Yokomaku, Y., Sugimoto, T., Kume, S., Araki, S., Isshiki, K., Chin-Kanasaki, M., Sakaguchi, M., Nitta, N., Haneda, M., Koya, D., Uzu, T., Kashiwagi, A
  • Journal Title: J Am Soc Nephrol 19(2) Pages: 321-328
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] アシアロエリスロポエチンは、造影剤腎症の発症を抑制する (2007)
  • Author(s): 横幕由喜代, 他
  • Organizer: 第50回日本腎臓学会学術総会
  • Place of Presentation: 浜松
  • Year and Date: 2007-05-27
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Asialoerythropoietin prevents contrast-induced nephropathy (2007)
  • Author(s): Yokomaku, Y., Sugimoto, T., Kume, S., Sakaguchi, M., Chin-Kanasaki, M., Isshiki, K., Araki, S., Higuchi, M., Haneda, M., Koya, D., Uzu, T
  • Organizer: The 50st Annual Meeting Japanese Society of Nephrology
  • Place of Presentation: Hamamatu
  • Year and Date: 2007-05-27
  • Description: 「研究成果報告書概要(欧文)」より