Eendoplasmic reticulum stress is involved in the pathogenesisi of polycystic kidneydiease

• Project/Area Number: 21591050
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Clinical research Center, Chiba-East National Hospital, National Hospital Organization
• Principal Investigator: KOBAYASHI Katsuki 独立行政法人国立病院機構(千葉東病院臨床研究センター), 遺伝子解析, 診断研究室長 (40415451)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: AQP11 / ERストレス / 多発性嚢胞腎 / CFTR / AQPll

Research Abstract

We initially noticed that the proximal tubule cells at the surface to mid cortex becamevacuolated and apoptotic, whereas those deeper within the cortex proliferatedvigorously and eventually formed cysts. Then by staining kidneys with antibodiesagainst ER-stress-responsive factors, we recognized a strong activation of CHOPexpression in the vacuolated and apoptotic proximal tubule cells. This was evidencethat the apoptosis was the result of ER stress. In contrast to CHOP, GRP78 expressionwas augmented exclusively in the deep-cortex proximal tubule cells, a sign of a similarinduction of ER stress in these cells. Yet in these cells, the ER stress was followed bycellular proliferation.

Research Products

• [Presentation] Disruption of Mouse AQP11 Induces Endoplasmic Reticulum Stress, Followedby Apoptosis and Cellular Proliferation, in the Proximal Tubule Cells of the Kidney (2011)
  • Author(s): Katsuki Kobayashi, Sei Sasaki
  • Organizer: ASN Renal Week 2010
  • Place of Presentation: 米国コロラド州デンバー
  • Year and Date: 2011-11-19
• [Presentation] Disruption of Mouse AQP11 Induces Endoplasmic Reticulum Stress, Followed by Apoptosis and Cellular Proliferation, in the Proximal Tubule Cells of the Kidney (2011)
  • Author(s): Katsuki Kobayashi, Sei Sasaki
  • Organizer: ASN Renal Week 2010
  • Place of Presentation: 米国コロラド州デンバー
  • Year and Date: 2011-11-19
• [Presentation] CFTRis Highly Expressed in the Cyst-Lining Epithelial Cells ofthe AQP11 Knockout MouseKidney (2011)
  • Author(s): Denver, COKatsuki Kobayashi, et al
  • Organizer: Kidney Week
  • Place of Presentation: Philadelphia, PA
• [Presentation] hly Expressed in the Cyst-Lininng Epithelial Cells of the AQP11 Knockout M (2011)
  • Author(s): Katsuki Kobayashi, et al
  • Organizer: Kidney Week 2011
  • Place of Presentation: Philadelphia, PA
• [Presentation] AQP11の欠損は近位尿細管の異なる部位にアポトーシスと細胞増殖を別々に誘導する (2010)
  • Author(s): 小林克樹、品田絵美、内田信一、佐々木成
  • Organizer: 第53回日本腎臓学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-18
• [Presentation] AQP11の欠損は近位尿細管の異なる部位にアポトーシスと細胞増殖を別々に誘導する。 (2010)
  • Author(s): 小林克樹、品田絵美、内田信一、佐々木成
  • Organizer: 第53回日本腎臓学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-18
• [Presentation] Disruption of Mouse AQP11Induces Endoplasmic ReticulumStess, Followed by Apoptosisand Cellular Proliferation, in the Proximal Tubule Cells ofthe Kidney (2010)
  • Author(s): San Diego CAKatsuki Kobayashi, et al
  • Organizer: Renal Week
  • Place of Presentation: Denver, CO
• [Presentation] Lossof Aquaporin-11 Causes Both theApoptosis and the Enhanced CellProliferation of the RenalProximal tubule Cells (2009)
  • Author(s): Katsuki Kobayashi, et al
  • Organizer: Renal Week
  • Place of Presentation: San Diego CA
• [Book] 腎臓内科学 (2010)
  • Author(s): 佐々木成(編者)
  • Total Pages: 209
  • Publisher: シュプリンガー・ジャパン