Investigating a new therapeutic approach from autophagy-deficient associated protein

• Project/Area Number: 24659416
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: ISAKA Yoshitaka 大阪大学, 医学(系)研究科(研究院), 准教授 (00379166)
• Co-Investigator(Kenkyū-buntansha): TAKABATAKE Yoshitsugu 大阪大学, 大学院医学系研究科, 助教 (30403075)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腎臓内科学 / オートファジー / 尿細管傷害 / 活性酸素 / ミトコンドリア / リソソーム / 酸化ストレス / 急性腎障害 / 腎臓内科 / アシドーシス / 尿細管 / 炎症 / 高尿酸血症

Outline of Final Research Achievements

Macroautophagy is a highly evolutionally concerved degradation process by which cytosolic materials and damaged organelles are broken down to their basic component. We investigated the role of autophagy in proximal tubular epithelial cells using autophagy- deficient mice and cultured tubular cells. Autphagy guarded proximal tubular cells against kidney injury by cisplatin, cyclosporine, urate crystal, or metabolic acidosis. The protective mechanism is to alleviate DNA damage, reactive oxygen species by eliminating damaged mitochondria, ruptured lysosomes, or aggregated protein. In addition, autophagy acts to ameliorate the chronic metabolic stress induced by cyclosporine or metabolic acidosis. These data provide new therapeutic perspective in chronic kidney diseases.

Research Products

• [Journal Article] Autophagic Clearance of Mitochondria in the Kidney Copes with Metabolic Acidosis. (2014)
  • Author(s): Namba T, Takabatake Y, Kimura T, Takahashi A, Yamamoto T, Matsuda J, Kitamura H, Niimura F, Matsusaka T, Iwatani H, Matsui I, Kaimori J, Kioka H, Isaka Y, Rakugi H.
  • Journal Title: J Am Soc Nephrol. Volume: 25・10 Issue: 10 Pages: 2254-66
  • DOI: 10.1681/asn.2013090986
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autophagy protects kidney proximal tubule epithelial cells from mitochondrial metabolic stress (2013)
  • Author(s): Kimura, T., Takahashi, A., Takabatake, Y., Namba, T, Yamamoto, T., Kaimori, J.Y., Matsui, I., Kitamura, H., Niimura, F., Matsusaka T., Soga, T., Rakugi, H., Isaka, Y.
  • Journal Title: Autophagy Volume: 9 Issue: 11 Pages: 1876-1886
  • DOI: 10.4161/auto.25418
  • Peer Reviewed
• [Journal Article] Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury (2013)
  • Author(s): Maejima I, Takahashi A, Omori H, Kimura T, Takabatake Y, Saitoh T, Yamamoto A, Hamasaki M, Noda T, Isaka Y, Yoshimori T
  • Journal Title: EMBO J. Volume: 32 Issue: 17 Pages: 2336-47
  • DOI: 10.1038/emboj.2013.171
  • Peer Reviewed / Open Access
• [Journal Article] Chloroquine in cancer therapy: a double-edged sword of autophagy (2013)
  • Author(s): Kimura T, Takabatake Y, Takahashi A, Isaka Y
  • Journal Title: Cancer Res Volume: 73 Issue: 1 Pages: 3-7
  • DOI: 10.1158/0008-5472.can-12-2464
  • Peer Reviewed
• [Journal Article] The protective role of autophagy against aging and acute ischemic injury in kidney proximal tubular cells. (2012)
  • Author(s): Isaka Y, Kimura T, Takabatake Y.
  • Journal Title: Autophagy Volume: 7 Pages: 1085-1087
  • Peer Reviewed
• [Journal Article] Autophagy guards against cisplatin-induced acute kidney injury (2012)
  • Author(s): 高橋篤史,松阪泰二、新村文男, 他
  • Journal Title: Am J Pathol Volume: 180 Issue: 2 Pages: 517-525
  • DOI: 10.1016/j.ajpath.2011.11.001
  • Peer Reviewed
• [Presentation] 慢性腎臓病におけるオートファジーと慢性炎症の接点 (2014)
  • Author(s): 猪阪善隆
  • Organizer: 腎不全研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-13
  • Invited
• [Presentation] オートファジーとミトファジー (2014)
  • Author(s): 猪阪善隆
  • Organizer: 抗加齢医学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-06
  • Invited