Identification of new therapeutic target for chronic kidney diseases

• Project/Area Number: 23890085
• 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: KUME Shinji 滋賀医科大学, 医学部, 特任助教 (00452235)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 慢性腎臓病 / 肥満 / 老化 / 医学

Research Abstract

In glomerular diseases, reducing proteinuria is considered as a principal therapeutic target to improve renal outcomes.. Unfortunately, however, some patients develop treatment-resistant proteinuria, resulting in end stage renal disease. In these patients, protecting proximal tubular epithelial cells (PTECs) against proteinuria may be the next therapeutic target to improve renal outcomes. Obesity and aging are independent risk factors for a rapid decline in renal function inpatients with glomerular diseases. Since the severity of proteinuria-induced tubulointerstitial lesions is correlated with renal outcomes, obesity and aging may exacerbate proteinuria-induced tubulointerstitial lesions. If so, identifying the molecular mechanisms underlying obesity- and aging-mediated PTEC vulnerability may lead to new therapy that improves renal outcome in patients with proteinuria. We thus tried to identify a new therapeutic candidate genes by using cDNA microarray analysis in the kidney samples from obese and aged mice with proteinuria. In this study, we have identified a new candidate gene involved in the mechanism underlying obesity- and aging-mediated worsening of proteinuria-induced tubulointerstitial lesion

Research Products

• [Journal Article] Anti-aging molecule, Sirt1: a novel therapeutic target for diabetic nephropathy (2013)
  • Author(s): Kume S.
  • Journal Title: Arch Pharm Res. Volume: 36(2) Issue: 2 Pages: 230-6
  • DOI: 10.1007/s12272-013-0019-4
  • Peer Reviewed
• [Journal Article] Sirtuins and renal diseases: relationship with aging and diabetic nephropathy (2013)
  • Author(s): Kitada M.
  • Journal Title: Clin Sci (Lond) Volume: 124(3) Issue: 3 Pages: 153-64
  • DOI: 10.1042/cs20120190
  • Peer Reviewed
• [Journal Article] Kume S, Uzu T, Maegawa H, Koya D (2012)
  • Author(s): Kume S, Uzu T, Maegawa H, Koya D
  • Journal Title: Clin Exp Nephrol Volume: 16 Issue: 6 Pages: 827-832
  • DOI: 10.1007/s10157-012-0695-2
  • Peer Reviewed
• [Journal Article] Emerging role of autophagy in kidney function, diseases and aging (2012)
  • Author(s): Huber TB, Edelstein CL, Hartleben B, Inoki K, Jiang M, Koya D, Kume S, Lieberthal W, Pallet N, Quiroga A, Ravichandran K, Susztak K, Yoshida S, Dong Z.
  • Journal Title: Autophagy Volume: 8(7) Issue: 7 Pages: 1009-1031
  • DOI: 10.4161/auto.19821
  • Peer Reviewed
• [Journal Article] Nutrient sensing, autophagy, and diabetic nephropathy (2012)
  • Author(s): Kume S, Thomas MC, Koya D
  • Journal Title: Diabetes Volume: 61(1) Issue: 1 Pages: 23-9
  • DOI: 10.2337/db11-0555
  • Peer Reviewed
• [Journal Article] Autophagy as a therapeutic target in diabetic nephropathy (2012)
  • Author(s): Tanaka Y, Kume S, Kitada M, Kanasaki K, Uzu T, Maegawa H, Koya D
  • Journal Title: Exp Diabetes Res Volume: 2012:628978 Pages: 1-12
  • DOI: 10.1155/2012/628978
  • Peer Reviewed
• [Journal Article] Nutrient sensing, autophagy, and diabetic nephropathy (2012)
  • Author(s): Kume S, et al
  • Journal Title: Diabetes Volume: 61(1) Pages: 23-29
  • Peer Reviewed
• [Journal Article] GW501516, a PPARδ agonist, ameliorates tubulointerstitial in flammation in proteinuric kidney disease via inhibition of TAK1-NFkB pathway in mice (2011)
  • Author(s): Yang X, Kume S, Tanaka Y, Isshiki K, Araki S, Chin-Kanasaki M, Sugimoto T, Koya D, Haneda M, Sugaya T, Li D, Han P, Nishio Y, Kashiwagi A, Maegawa H, Uzu T
  • Journal Title: PLoS One. Volume: 6 Issue: 9 Pages: e25271-e25271
  • DOI: 10.1371/journal.pone.0025271
  • Peer Reviewed
• [Journal Article] SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells. (2011)
  • Author(s): Koyama T, Kume S, Koya D, Araki S, Isshiki K, Chin-Kanasaki M, Sugimoto T, Haneda M, Sugaya T, Kashiwagi A, Maegawa H, Uzu T.
  • Journal Title: Free Radic Biol Med Volume: 51(6) Pages: 1258-67
  • Peer Reviewed
• [Journal Article] Fenofibrate, a PPARα agonist, has renoprotective effects in mice by enhancing renal lipolysis (2011)
  • Author(s): Tanaka Y, Kume S, Araki S, Isshiki K, Chin-Kanasaki M, Sakaguchi M, Sugimoto T, Koya D, Haneda M, Kashiwagi A, Maegawa H, Uzu T
  • Journal Title: Kidney Int Volume: 79(8) Issue: 8 Pages: 871-82
  • DOI: 10.1038/ki.2010.530
  • Peer Reviewed
• [Journal Article] Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn-SOD dysfunction in AMPK/SIRT1-independent pathway (2011)
  • Author(s): Kitada M, Kume S, Imaizumi N, Koya D
  • Journal Title: Diabetes Volume: 60(2) Issue: 2 Pages: 634-43
  • DOI: 10.2337/db10-0386
  • Peer Reviewed
• [Journal Article] Sirt1 in Diabetic Nephropathy (2011)
  • Author(s): 久米真司, 他
  • Journal Title: 日本腎臓学会誌 Volume: 53(7) Pages: 1010-1015
  • NAID: 10030343488
• [Journal Article] GW501516, a PPARδ agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disesse via inhibition of TAK1-NFκB pathway in (2011)
  • Author(s): Xu Y, Kume S, et al
  • Journal Title: PLoS ONE Volume: 6(9)
  • Peer Reviewed
• [Presentation] (2012)
  • Author(s): 久米真司
  • Organizer: 第12回日本抗加齢医学会総会
  • Place of Presentation: 横浜
• [Presentation] (2012)
  • Author(s): 久米真司
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] (2012)
  • Author(s): 久米真司
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] Autophagy deficiency in obese and aging mice exacerbates proteinuria-associated renal tubulointerstitial lesion (2011)
  • Author(s): Kume S.
  • Organizer: 71th Scientific Sessions
  • Place of Presentation: SanDiego (American Diabetes Association).
• [Presentation] Autophagy in diabetic nephropathy (2011)
  • Author(s): Kume S
  • Organizer: The 20th Summer Symposium & Workshop
  • Place of Presentation: in Seoul (Korea Diabetes Association)
• [Presentation] 肥満・メタボリックシンドロームと慢性炎症 腎脂肪毒性と慢性炎症 (2011)
  • Author(s): 久米真司,古家大祐, 前川聡
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 兵庫
• [Presentation] 基礎研究から臨床への応用 慢性腎臓病とオートファジー (2011)
  • Author(s): 久米真司
  • Organizer: 第41回 日本腎臓学会西部学術大会
  • Place of Presentation: 徳島
• [Presentation] カロリー制限による加齢腎病変の保護作用 (2011)
  • Author(s): 久米真司
  • Organizer: 第11回日本抗加齢医学会総会
  • Place of Presentation: 京都
• [Book] 腎臓におけるオートファジーの制御と病態への関与Annual Review 腎臓2012 巻 (2012)
  • Author(s): 久米真司, 古家大祐, 前川聡
  • Publisher: Annual Review
• [Book] カロリー制限による腎保護効果における抗老化分子Sirt1-オートファジー経路の意義 (2011)
  • Author(s): 久米真司, 前川聡, 古家大祐
  • Publisher: Adiposcience
• [Book] Sirt1 とカロリー制限 (2011)
  • Author(s): 久米真司, 前川聡, 古家大祐
  • Publisher: Annual Review 2011
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~hqmed3/snai/kenkyu3/supervisorydr.html