Abnormalities in cell polarity in polycystic kidney disease

• Project/Area Number: 20790739
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Wakayama Medical University
• Principal Investigator: TOGAWA Hiroko Wakayama Medical University, 医学部, 助教 (30445093)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 多発性嚢胞腎 / 遺伝性腎疾患 / 上皮間葉移行 / PCKラット / 間葉系マーカー / E-カドヘリン / βカテニン / エンドサイトーシス / 細胞極性 / Na^+-K^+-ATPase / Na^<+->K^<+->ATPase

Research Abstract

We examined the expression of cell adhesion molecules and mesenchymal markers to clarify a loss of cell polarity in PCK rat, an ARPKD model with a mutation in the orthologue of human PKHDJ. E-cadherin and β-catenin expression levels in cystic tubule was attenuated and localized to lateral cell-cell contacts according to cyst enlargement in PCK rats. Some epithelial cells in large cysts derived from these segments of nephron, especially in adjacent fibrotic area, showed positive immunoreactivity of vimentin and fibronectin. Vimentin and fibronectin positive cells are increased in fibrotic area around cyst. In conclusions, these findings suggested that EMT is involved in pathophysiology of PKD.

Research Products

• [Journal Article] Epithelial-to-mesenchymal transition in cyst-lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease. (2011)
  • Author(s): Togawa H, Nakanishi K, Mukaiyama H, Hama T, Shima Y, Sako M, Miyajima M, Nozu K, Nishii K, Nagao S, Takahashi H, Iijima K, Yoshikawa N.
  • Journal Title: Am J Physiol Renal Physiol. 300(2)
  • Peer Reviewed
• [Journal Article] Epithelial-to-mesenchymal transition in cyst-lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease. (2011)
  • Author(s): Togawa H
  • Journal Title: Am J Physiol Renal Physiol Volume: 300
  • Peer Reviewed
• [Journal Article] Increased chymase-positive mast cells in children with crescentic glomerulonephritis. (2009)
  • Author(s): Togawa H
  • Journal Title: Pediatric Nephrology 24 Pages: 1071-1075
  • Peer Reviewed
• [Journal Article] Increased chymase-positive mast cells in children with crescentic glomerulonephritis (2009)
  • Author(s): Togawa H
  • Journal Title: Pediatr Nephrol 24 Pages: 1071-1075
  • Peer Reviewed
• [Journal Article] Membranous nephropathy associated with thyroid-peroxidase antigen (2009)
  • Author(s): Shima Y
  • Journal Title: Pediatr Nephrol 24 Pages: 605-608
  • Peer Reviewed
• [Journal Article] Improved renal survival in Japanese children with IgA nephropathy (2008)
  • Author(s): Yata N
  • Journal Title: Pediatr Nephrol 23 Pages: 905-912
  • Peer Reviewed
• [Presentation] Epithelial-to-Mesenchymal Transition (EMT) in cpk Mouse, a Model of ARPKD. (2010)
  • Author(s): Togawa H, Nakanishi K, Mukaiyama H, Hama T, Shima Y, Miyajima M, Nozu K, Takahashi H, Nagao S, Iijima K, Yoshikawa N.
  • Organizer: 43^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Denver, USA
• [Presentation] 常染色体劣性多発性嚢胞腎(ARPKD)モデルcpkマウスの尿細管上皮細胞における上皮間葉移行(EMT) (2010)
  • Author(s): 戸川寛子, 中西浩一, 島友子, 佐古まゆみ, 向山弘展, 宮嶋正康, 野津寛大, 吉原大輔, 長尾枝澄香, 飯島一誠, 吉川徳茂
  • Organizer: 第44回日本小児腎臓病学会学術集会
  • Place of Presentation: 大阪
• [Presentation] ヒトARPKDと相同遺伝子変異を有するPCK ratにおける上皮間葉移行 (2010)
  • Author(s): 戸川寛子, 中西浩一, 島友子, 佐古まゆみ, 向山弘展, 宮嶋正康, 野津寛大, 吉原大輔, 長尾枝澄香, 飯島一誠, 吉川徳茂
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸
• [Presentation] ARPKD相同遺伝子ラットモデルの尿細管上皮細胞における上皮間葉移行(EMT). (2009)
  • Author(s): 戸川寛子
  • Organizer: 第44回日本小児腎臓病学会学術集会
  • Place of Presentation: 一橋記念講堂・学術センター(東京都)
  • Year and Date: 2009-06-27
• [Presentation] ヒトARPKD相同遺伝子ラットモデルにおける尿細管部位特異的嚢胞形成. (2009)
  • Author(s): 戸川寛子
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: パシイフイコ横浜(神奈川県)
  • Year and Date: 2009-06-04
• [Presentation] Snaill Is Involved in Epithelial-to-Mesenchymal Transition (EMT) in Cyst-Lining Epithelial. (2009)
  • Author(s): Togawa H, Nakanishi K, Shima Y, Sako M, Miyajima M, Nozu K, Iijima K, Yoshihara D, Nagao S, Yoshikawa N
  • Organizer: 42^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
• [Presentation] ARPKD相同遺伝子ラットモデルの尿細管上皮細胞における上皮間葉移行(EMT) (2009)
  • Author(s): 戸川寛子, 中西浩一, 島友子, 佐古まゆみ. 宮嶋正康, 野津寛大, 飯島一誠, 吉原大輔, 長尾枝澄香, 吉川徳茂
  • Organizer: 第44回日本小児腎臓病学会学術集会
  • Place of Presentation: 東京
• [Presentation] ヒトARPKD相同遺伝子ラットモデルにおける尿細管部位特異的嚢胞形成 (2009)
  • Author(s): 戸川寛子, 中西浩一, 島友子, 佐古まゆみ, 宮嶋正康, 西井一宏, 長尾枝澄香, 高橋久英, 吉川徳茂
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Snail1 Is Involved in Epithelial-to-Mesenchymal Transition (EMT) in Cyst-Lining Epithelial Cells in PCK Rat. (2009)
  • Author(s): Togawa H
  • Organizer: 42^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
• [Presentation] Epithelial-to-mesenchymal transition (EMT) in cyst-lining epithelial cells in PCK rat (2008)
  • Author(s): Hiroko Togawa
  • Organizer: The 41th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-07
• [Presentation] Epithelial-to-Mesenchymal Transition in Cyst-Lining Epithelial Cells in PCK Rat. J Am Soc Nephrol 19 : 362A (2008)
  • Author(s): Togawa H, Nakanishi K, Obana M, Shima Y, Miyajima M, Nozu K, Iijima K, Nishi K, Nagao S, Takahashi H, Yoshikawa N
  • Organizer: 2008 41^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
• [Presentation] 多発性嚢胞腎(PKD)の嚢胞形成にはE-cadherin/β-cateninの破綻が関与する (2008)
  • Author(s): 戸川寛子, 中西浩一, 佐古まゆみ, 尾鼻美奈, 島友子, 宮嶋正康, 西井一宏, 長尾枝澄香, 高橋久英, 吉川徳茂
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡