Effect of TGF-β on WT1 expression in podocyte.

• Project/Area Number: 23790930
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Gunma University
• Principal Investigator: SAKAIRI Toru 群馬大学, 医学部, 助教 (20455976)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 糖尿病性腎症 / 巣状糸球体硬化症 / 糸球体上皮細胞 / TGF-beta1 / WT1 / TGF-beta / Wilms tumor 1 / TGF-beta 1 / podocyte

Research Abstract

TGF-beta1 is involved in diabetes nephropathy and focal segmental glomerulonephritis. Transcriptional factor Wilms tumor suppressor gene (WT1) is essential for normal function of podocytes. We found that TGF-beta1 reduces WT1 expression in both cultured humanpodocytes and mouse podocytes. Using the cultured podocytes, we identified following mechanisms by which TGF-beta1 suppress WT1 expression. First, Smad4 mediates a decrease in WT1 expression by TGF-beta1. Second, TGF-beta1 caused DNA methylation in promoter region of the podocytes. Our results indicate that diverse pathways contribute to the TGF-beta1-induced WT1 reduction that may result in podocyte injury.

Research Products

• [Journal Article] TGF-beta1 reduces Wilms' tumor suppressor gene expression in podocytes (2011)
  • Author(s): Sakairi T, Abe Y, Kopp JB
  • Journal Title: Nephrol DialTransplant Volume: 26(9) Pages: 2746-52
  • Peer Reviewed
• [Journal Article] TGF-beta1 reduces Wilms' tumor suppressor gene expression in podocytes. (2011)
  • Author(s): Sakairi T, Abe Y, Kopp JB.
  • Journal Title: Nephrol Dial Transplant Volume: 26 Issue: 9 Pages: 2746-2752
  • DOI: 10.1093/ndt/gfr061
  • Peer Reviewed
• [Presentation] miR-143 contributes to podocyte injury induced by TGF-betal (2011)
  • Author(s): Sakairi T, Abe Y, Hiromura K, TakahashiS, Hamatani H, Nojima Y, and Kopp JB
  • Organizer: The 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
• [Presentation] Transforming Growth Factor (TGF)-β1 Induced DNA Methylation of Wilms' Tumor Suppressor Gene (WT1) Promoter in Human Podocytes (2011)
  • Author(s): Hamatani H, Hiromura K, Sakairi T, Takahashi S, Ikeuchi H, Maeshima A, and Nojima Y
  • Organizer: The 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
• [Presentation] miR-143 contributes to podocyte injury induced by TGF-beta1 (2011)
  • Author(s): Sakairi T, Abe Y, Hiromura K, Takahashi S, Hamatani H, Nojima Y, and Kopp JB
  • Organizer: The 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
• [Presentation] Transforming Growth Factor (TGF)-β1 Induced DNA Methylation of Wilms’ Tumor Suppressor Gene (WT1) Promoter in Human Podocytes. (2011)
  • Author(s): Hamatani H, Hiromura K, Sakairi T, Takahashi S, Ikeuchi H, Maeshima A, Nojima Y.
  • Organizer: The 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
• [Presentation] A Novel Case of Nephrotic Syndrome Caused by Immune-Mediated Severe LCAT Deficiency. (2011)
  • Author(s): Takahashi S, Hiromura K, Tsukida M, Ohishi Y, Hamatani H, Sakurai N, Sakairi T, Ikeuchi H, Maeshima A, Kuroiwa T, Nagata M, and Nojima Y.
  • Organizer: The 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
• [Presentation] TGF-beta1 は、糸球体上皮細胞におけるWT1の発現を抑制する (2011)
  • Author(s): 坂入 徹、阿部 祥英、廣村 桂樹、高橋 哲史、浜谷 博子、櫻井 則之、池内 秀和、野島 美久、Kopp Jeffrey
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] SIRPαシグナル経路の遮断は糖尿病性腎症を増悪させる (2011)
  • Author(s): 高橋 哲史1、廣村 桂樹1、浜谷 博子1、加藤 麻衣1、坂入 徹、櫻井 則之、池内 秀和、前嶋 明人、黒岩 卓、青木 武生、大西 浩史、的崎 尚、野島 美久
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 後天性LCAT欠損によるネフローゼ症候群の1例とその機序解析 (2011)
  • Author(s): 高橋 哲史、廣村 桂樹、月田 真祐子、大石 裕子、浜谷 博子、櫻井 則之、坂入 徹、池内 秀和、前嶋 明人、黒岩 卓、長田 道夫、野島 美久
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] ループス腎炎の寛解導入における、タクロリムス（TAC）とミコフェノール酸モフェチル（MMF）の併用療法の試み (2011)
  • Author(s): 池内 秀和、廣村 桂樹、高橋 哲史、月田 真祐子、内山 和彦、櫻井 則之、坂入 徹、前嶋 明人、黒岩 卓、野島 美久
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 複数のThymidineアナログを用いたlabel-retaining cells（LRCs）の検討 (2011)
  • Author(s): 前嶋 明人、宮 政明、三島 敬一郎、櫻井 則之、池内 秀和、坂入 徹、黒岩 卓、廣村 桂樹、野島 美久
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] TGF-beta reduces Wilms tumor 1 expression in podocytes in vitro and in vivo (2010)
  • Author(s): Sakairi T, Abe Y, and Kopp JB
  • Organizer: The 43th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Denver, USA
• [Remarks]
• [Remarks]
  • URL: http://mcs.dept.med.gunma-u.ac.jp/index.html