Role of autophagy in the pathogenesis of diabetic nephropathy

• Project/Area Number: 24890089
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Shiga University of Medical Science
• Principal Investigator: MORITA Yoshikata 滋賀医科大学, 医学部, 特任助教 (40636130)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 糖尿病性腎症 / 糸球体上皮細胞 / 腎臓病学 / オートファジー

Research Abstract

Diabetic nephropathy is a leading cause of end stage of renal disease. Thus new therapeutic strategy is urgently required. Hyperactivation of mTORC1 signal in podocytes has been reported to be strongly associated with the progression of diabetic nephropathy. However, the detailed mechanism underlying diabetes-related mTORC1 activation has remained unclear. In this study, we have revealed that saturated fatty acid is a potent activator of mTORC1 and subsequent inducer of apoptosis in podocytes. Furthermore, autophagy insufficiency related to mTORC1 hayperactivation was strongly associated with the progression of podocyte dysfunction and subsequent proteinuria in mice. The results suggest that inhibition of free fatty acid-mediated mTORC1 activation and activation of autophagy in podocytes are new therapeutic strategies for diabetic nephropathy.

Research Products

• [Journal Article] Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization and apoptosis in podocytes (2014)
  • Author(s): Yasuda M, Tanaka Y, Kume S, Morita Y, Chin-Kanasaki M, Araki H, Isshiki K, Araki SI, Koya D, Haneda M, Kashiwagi A, Maegawa H, Uzu T
  • Journal Title: Biochim Biophys Acta. Volume: 1842(7) Pages: 1097-1108
  • Peer Reviewed
• [Journal Article] Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization and apoptosis in podocytes. (2014)
  • Author(s): Yasuda M, Tanaka Y, Kume S, Morita Y, Chin-Kanasaki M, Araki H, Isshiki K, Araki SI, Koya D, Haneda M, Kashiwagi A, Maegawa H, Uzu T.
  • Journal Title: Biochim Biophys Acta. Volume: 1842 Issue: 7 Pages: 1097-1108
  • DOI: 10.1016/j.bbadis.2014.04.001
  • Peer Reviewed / Open Access
• [Presentation] 糖尿病性腎症発症における糸球体上皮細胞オートファジーの役割 (2013)
  • Author(s): 安田真子,田川安都子,久米真司,田中敬,森田善方,荒木久澄,一色啓二,荒木信一,宇津貴,前川聡
  • Organizer: 第25回日本糖尿病性腎症研究会
  • Place of Presentation: 東京(口頭発表)
• [Presentation] 飽和脂肪酸はmTORC1過剰亢進を介し糸球体上皮細胞のアポトーシスを惹起する (2013)
  • Author(s): 安田真子,田中敬,久米真司,森田善方,荒木久澄,一色啓二,荒木信一,古家大祐,羽田勝計,柏木厚典,宇津貴,前川聡
  • Organizer: 第28回日本糖尿病合併症学会
  • Place of Presentation: 旭川(口頭発表)
• [Presentation] 飽和脂肪酸はmTORC1過剰亢進を介し糸球体上皮細胞のアポトーシスを惹起する. (2013)
  • Author(s): 安田 真子, 田中 敬, 久米 真司, 森田 善方, 荒木 久澄, 一色 啓二, 荒木 信一, 古家 大祐, 羽田 勝計, 柏木 厚典, 宇津 貴, 前川 聡.
  • Organizer: 第28回日本糖尿病合併症学会
  • Place of Presentation: 旭川