Role of CTGF on podocytes and tubulointerstitium in chronic kidney disease.

• Project/Area Number: 21790806
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: YOKOI Hideki Kyoto University, 医学研究科, 特定助教 (90378779)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 腎臓学 / CTGF / Cre / ポドサイト / loxP / 慢性腎臓病 / nephrin / 細胞外基質 / TGF-beta / 細胞外基

Research Abstract

CTGF is a growth factor strongly induced by TGF-β and has a profibrotic effects. Neonatal death of CTGF knockout mice by the deformity of the ribs makes the evaluation of the role of CTGF in chronic kidney disease difficult. To solve these problems, we constructed CTGF floxed mice. We generated systemic inducible CTGF knockdown mice and podocyte-specific CTGF knockout mice to investigate the role of CTGF in chronic kidney disease.
1. Systemic tamoxifen inducible CTGF knockdown mice.
We crossed RosaCreER^<T2> mice, which activate Cre recombinase by the stimulation of tamoxifen, with CTGF floxed mice to generate systemic inducible CTGF knockdown mice. Although expression of CTGF in the kidney, liver and heart of systemic inducible CTGF knockdown mice is reduced by 80-90%, histological examination showed normal phenotype. Gene array were performed to find candidate gene on the CTGF-downstream pathway.
2. Diabetic nephropathy in podocyte-specific CTGF knockout mice.
We generated podocyte-specific CTGF knockout mice. Although expression of CTGF mRNA in glomeruli was decreased by 87%, the kidney was normal and urinary albumin excretion was within normal range. Next, we generated type 1 diabetic mice by injection of streptozotocin in podocyte-specific CTGF knockout mice. There is no significant difference between diabetic wild-type mice and diabetic podocyte-specific CTGF knockout mice in urinary albumin excretion and renal histology.

Research Products

• [Journal Article] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice (2010)
  • Author(s): Yokoi H, Kasahara M, Mukoyama M, Mori K, Kuwahara K, Fujikura J, Arai Y, Saito Y, Ogawa Y, Kuwabara T, Sugawara A, Nakao K.
  • Journal Title: Nephrol Dial Transplant 25 Pages: 2120-2124
  • Peer Reviewed
• [Journal Article] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice (2010)
  • Author(s): Ybkoi H., 他11名
  • Journal Title: Nephrol Dial Transplant Volume: 25 Pages: 2120-2124
  • Peer Reviewed
• [Journal Article] Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients. (2009)
  • Author(s): Kasahara M, Mori K, Satoh N, Kuwabara T, Yokoi H, Shimatsu A, Sugawara A, Mukoyama M, Nakao K.
  • Journal Title: Nephrol Dial Transplant 24 Pages: 2608-2609
  • Peer Reviewed
• [Journal Article] Reduction in urinary excretion of neutrophil gelatinase-associated lipocal in by angiotensin receptor blockers in hypertensive patients. (2009)
  • Author(s): Kasahara, et al.
  • Journal Title: Nephrol Dial Transplant 24 Pages: 2608-2609
  • Peer Reviewed
• [Journal Article] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice
  • Author(s): Yokoi, et al.
  • Journal Title: Nephrol Dial Transplant 2010(In press)
  • Peer Reviewed
• [Presentation] Podocyte-Specific Expression of Tamoxifen-inducible Cre Recombinase in Mice. (2010)
  • Author(s): Yokoi H, Kasahara M, Mukoyama M, Mori K, Kuwabara T, Sugawara A, Nakao K.
  • Organizer: 2010年米国腎臓病学会学術集会
  • Place of Presentation: デンバー、アメリカ
  • Year and Date: 2010-11-19
• [Presentation] Podocyte-specific expression of tsmoxifen-inducible Cre recombinase in mice (2010)
  • Author(s): Yokoi H., 他8名
  • Organizer: 米国腎臓学会学術集会
  • Place of Presentation: Denver, Coloxado, USA
  • Year and Date: 2010-11-19
• [Presentation] タモキシフェン誘導性糸球体上皮細胞特異的Cre過剰発現マウスの作成 (2010)
  • Author(s): 横井秀基、笠原正登、森潔、小川喜久、〓原孝成、齋藤陽子、今牧博貴、川西智子、古賀健一、石井輝、菅原照、向山政志、中尾一和
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-17
• [Presentation] Podocyte-Specific Expression of Tamoxifen-inducible Cre Recombinase in Mice. (2010)
  • Author(s): Yokoi H, Kasahara M, Mukoyama M, Mori K, Kuwahara T, Fujikura J, Arai Y, Saito Y, Ogawa Y, Kuwabara T, Imamaki H, Kawanishi T, Ishii A, Koga K, Sugawara A, Nakao K.
  • Organizer: 国際腎臓病学会 Nexus Symposium 2010
  • Place of Presentation: 京都
  • Year and Date: 2010-04-16
• [Presentation] シルニジピンの2型糖尿病性腎症モデルマウスに対する腎保護作用 (2009)
  • Author(s): 横井秀基
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-06-04
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