Disease specific therapy for polycystic kidney disease based on EMT

• Project/Area Number: 23791190
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Wakayama Medical University
• Principal Investigator: TOGAWA Hiroko 和歌山県立医科大学, 医学部, 助教 (30445093)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝性腎疾患 / 多発性嚢胞腎 / 上皮間葉移行 / CPKマウス / TGF-β / Smad3 / 疾患特異的治療 / TGF-β/Smad3 / 上皮間葉移行(EMT)

Research Abstract

Epithelial mesenchymal transition (EMT) is thought to be involved in pathophysiology of polycystic kidney disease (PKD). We determined a signal transduction of EMT in PKD in this study and examined possibility of pathophysiology-specific therapy that targeted the signal transduction.
In CPK mouse, qualitative rather than quantitative abnormality was present in the TGF-beta/Smad3 system, and enhanced expression of c-Myc by intranuclear pSmad3L/C effects through JNK/CDK4 was shown. Furthermore, we made Smad3 knock-out and CPK double mutant and examined changes of the disease phenotype by modification of Smad3. With these findings, we obtained the basic data for disease-specific therapy developments.

Research Products

• [Journal Article] 髄質嚢胞腎.腎臓症候群(第2版)-その他の腎臓疾患を含めて- (2012)
  • Author(s): 戸川寛子,中西浩一,吉川徳茂
  • Journal Title: 別冊日本臨床新領域別症候群シリーズ Volume: 17 Pages: 600-602
• [Presentation] 常染色体劣性多発性嚢胞腎の鑑別を要した3例 (2013)
  • Author(s): 浜武継,中西浩一,佐藤匡,向山弘展,戸川寛子,島友子,辻本弘,神波信次,吉川徳茂
  • Organizer: 第35回日本小児腎不全学会学術集会
  • Place of Presentation: 郡山
  • Year and Date: 2013-10-24
• [Presentation] cpkマウスARPKDモデルにおける病的Smad3リン酸化 (2013)
  • Author(s): 浜武継,中西浩一,向山弘展,戸川寛子,佐藤匡,島友子,宮嶋正康,野津寛大,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第21回嚢胞性腎疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-09-21
• [Presentation] cpkマウスにおける病的Smad3リン酸化 (2013)
  • Author(s): 浜武継,中西浩一,向山弘展,戸川寛子,佐藤匡,島友子,宮嶋正康,野津寛大,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第22回発達腎研究会
  • Place of Presentation: 高槻
  • Year and Date: 2013-09-14
• [Presentation] Smad3 Phosphorylated at Both Linker and COOH-Terminal Regions in Cyst-Lining Epithelia in cpk Mouse, a Model of ARPKD (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Togawa H, Sato M, Shima Y, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K, Yoshikawa N
  • Organizer: 46^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Possible contribution of fibrocytes to renal fibrosis in cpk mouse, a model of ARPKD (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Sato M, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: 15th Congress of the International Pediatric Nephrology Association
  • Place of Presentation: Shanghai, China
• [Presentation] cpkマウス多発性嚢胞腎モデル腎線維化におけるfibrocyteの関与 (2013)
  • Author(s): 浜武継,中西浩一,向山弘展,佐藤匡,戸川寛子,島友子,宮嶋正康,高橋久英,長尾静子,飯島一誠,吉川徳茂
  • Organizer: 第48回日本小児腎臓病学会学術集会
  • Place of Presentation: 徳島
• [Presentation] Smad3 Phosphorylated at Both Linker and COOH-Terminal Regions in Cyst-Lining Epithelia in cpk Mouse, a Model of ARPKD. (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Togawa H, Sato M, Shima Y, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K, Yoshikawa N.
  • Organizer: The 46th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Possible Contribution of Fibrocytes to Renal Fibrosis in Cpk Mouse, a Model of ARPKD (2012)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: 45^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
• [Presentation] cpkマウスにおける部位特定的リン酸化Smad3の発現 (2012)
  • Author(s): 向山弘展,中西浩一,浜武継,戸川寛子,島友子,宮嶋正康,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第47回日本小児腎臓病学会学術集会
  • Place of Presentation: 東京
• [Presentation] Possible Contribution of Fibrocytes to Renal Fibrosis in Cpk Mouse, a Model of ARPKD (2012)
  • Author(s): 1) Taketsugu Hama, Koichi Nakanishi, Hironobu Mukaiyama, Hiroko Togawa, Yuko Shima, Masayasu Miyajima, Hisahide Takahashi, Shizuko Nagao, Kazumoto Iijima, Norishige Yoshikawa
  • Organizer: 45th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
• [Presentation] cpkマウスにおける部位特定的リン酸化Smad3の発現 (2011)
  • Author(s): 浜武継,中西浩一,向山弘展,戸川寛子,島友子,宮嶋正康,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第19回嚢胞性腎疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-11
• [Presentation] Acceleration of Smad3 phosphorylation at linker regions via c-Jun NH2-terminal kinase (JNK) in cyst-lining epithelial cells in cpk mouse, a model of ARPKD (2011)
  • Author(s): Mukaiyama H, Nakanishi K, Hama T, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: 44^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
• [Presentation] cpkマウスARPKDモデルにおける上皮間葉移行(EMT) (2011)
  • Author(s): 向山弘展,中西浩一,戸川寛子,濵武継,島友子,宮嶋正康,吉原大輔,長尾枝澄香,高橋久英,飯島一誠,吉川徳茂
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] cpkマウスARPKDモデルにおける上皮間葉移行(EMT) (2011)
  • Author(s): 向山弘展,中西浩一,戸川寛子,濵武継,島友子,宮嶋正康,吉原大輔,長尾枝澄香,高橋久英,飯島一誠,吉川徳茂
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Acceleration of Smad3 phosphorylation at linker regions via c-Jun NH2-terminal kinase (JNK) in cyst-lining epithelial cells in cpk mouse, a model of ARPKD (2011)
  • Author(s): Mukaiyama H, Nakanishi K, Hama T, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: The 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia
• [Presentation] cpkマウスにおける病的Smad3リン酸化
  • Author(s): 浜武継, 中西浩一, 向山弘展, 戸川寛子, 佐藤匡, 島 友子, 宮嶋正康, 野津寛大, 高橋久英, 長尾枝澄香, 飯島一誠, 吉川徳茂
  • Organizer: 第22回発達腎研究会
  • Place of Presentation: 高槻
• [Presentation] cpkマウスARPKDモデルにおける病的Smad3リン酸化
  • Author(s): 浜武継, 中西浩一, 向山弘展, 戸川寛子, 佐藤匡, 島 友子, 宮嶋正康, 野津寛大, 高橋久英, 長尾枝澄香, 飯島一誠, 吉川徳茂
  • Organizer: 第21回嚢胞性腎疾患研究会
  • Place of Presentation: 東京
• [Presentation] 常染色体劣性多発性嚢胞腎の鑑別を要した3例
  • Author(s): 浜武継, 中西浩一, 佐藤匡, 向山弘展, 戸川寛子, 島友子, 辻本弘, 神波信次, 吉川徳茂
  • Organizer: 第35回日本小児腎不全学会学術集会
  • Place of Presentation: 郡山