Investigation of a novel therapy for renal diseases by inhibiting CTGF

• Project/Area Number: 23591190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: YOKOI HIDEKI 京都大学, 医学(系)研究科(研究院), 特定病院助教 (90378779)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 内科 / 腎臓内科 / 糸球体腎炎 / 糸球体 / 腎炎 / マクロファージ / 線維化 / 腎不全 / 炎症 / 糖尿病性腎症 / 抗糸球体基底膜抗体腎炎 / ノックアウトマウス / floxedマウス / タモキシフェン

Research Abstract

Connective tissue growth factor (CTGF/CCN2) regulates signaling of other growth factors and promotes fibrosis. We examined the role of CTGF in diabetic nephropathy and in anti-glomerular basement membrane (anti-GBM) nephritis, using conditional CTGF knockout mice. Systemic inducible CTGF knockout (ROSA-CTGF cKO) mice and podocyte-specific CTGF knockout mice exhibited no apparent phenotypic changes in streptozotocin-induced diabetic nephropathy. In anti-GBM nephritis model, ROSA-CTGF cKO mice ameliorated proteinuria by 50%, macrophage infiltration in glomeruli by 40%, glomerular changes including crescentic formation, extracellular matrix deposition and thickness of GBM in electron microscopic analysis compared with control mice.

Research Products

• [Journal Article] Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases (2014)
  • Author(s): Kuwabara T, Mori K, Kasahara M, Yokoi H, Imamaki H, Ishii A, Koga K, Sugawara A, Yasuno S, Ueshima K, Morikawa T, Konishi Y, Imanishi M, Nishiyama A, Nakao K, Mukoyama M
  • Journal Title: PloS One Volume: 9 Issue: 2 Pages: e88942-e88942
  • DOI: 10.1371/journal.pone.0088942
  • Peer Reviewed / Open Access
• [Journal Article] Do statins play a role in renoprotection? (2014)
  • Author(s): Kasahara M, Nakagawa T, Yokoi H, Kuwabara T, Yasuno S, Mori K, Mukoyama M
  • Journal Title: Ueshima K. Clin Exp Nephrol Volume: 18 Issue: 2 Pages: 282-285
  • DOI: 10.1007/s10157-013-0928-z
  • Peer Reviewed
• [Journal Article] Do statins play a role in renoprotection? (2014)
  • Author(s): Kasahara M, Nakagawa T, Yokoi H, Kuwabara T, Yasuno S, Mori K, Mukoyama M, Ueshima K.
  • Journal Title: Clin Exp Nephrol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Peritoneal fibrosis and high transport are induced in mildly pre-injured peritoneum by 3,4-dideoxyglucosone-3-ene in mice (2013)
  • Author(s): Yokoi, H., Kasahara, M., Mori, K., Kuwabara, T., Toda, N., Yamada, R., Namoto, S., Yamamoto, T., Seki, N., Souma, N., Yamaguchi, T., Sugawara, A., Mukoyama, M., Nakao, K.
  • Journal Title: Peritoneal Dialysis International Volume: 33(2) Issue: 2 Pages: 143-154
  • DOI: 10.3747/pdi.2011.00033
  • Peer Reviewed
• [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury (2012)
  • Author(s): Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Kato Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Tokudome T, Kishimoto I, Sugawara A, Nakao K
  • Journal Title: J Am Soc Nephrol Volume: 23:1198-1209 Issue: 7 Pages: 1198-1209
  • DOI: 10.1681/asn.2011100985
  • Peer Reviewed
• [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice (2012)
  • Author(s): Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Ogawa Y, Imamaki H, Kawanishi T, Ishii A, Koga K, Mori KP, Kato Y, Sugawara A, Nakao K
  • Journal Title: Diabetologia Volume: 55:2256-2266 Issue: 8 Pages: 2256-2266
  • DOI: 10.1007/s00125-012-2578-1
  • NAID: 120004225542
  • Peer Reviewed
• [Journal Article] Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis (2012)
  • Author(s): Yokoi H, Nakao K, et al
  • Journal Title: Kidney Int. Volume: 81 Issue: 2 Pages: 160-169
  • DOI: 10.1038/ki.2011.305
  • Peer Reviewed
• [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by toll-like receptor 4 in mice (2012)
  • Author(s): Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Imamaki H, Kawanishi T, Ishii A, Koga K, Mori PK, Kato Y, Nakao K.
  • Journal Title: Diabetologia Volume: in press
  • Peer Reviewed
• [Presentation] Systemic Deletion of CTGF Ameliorates Anti-Glomerular Basement Membrane Nephritis with Reduction of Macrophage Infiltration (2013)
  • Author(s): N.Toda, H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, T.Matsusaka, K.Nakao, M.Mukoyama
  • Organizer: 米国腎臓病学会年次総会
  • Place of Presentation: 米国アトランタ
• [Presentation] 中尾一和抗糸球体基底膜(GBM)腎炎におけるCTGFの意義 (2013)
  • Author(s): 戸田尚宏、横井秀基、笠原正登、森潔、桒原孝成、今牧博貴、石井輝、古賀健一、森慶太、加藤有希子、大野祥子、菅原照、向山政志
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] 抗糸球体基底膜（GBM）腎炎におけるCTGFの意義 (2013)
  • Author(s): 戸田尚宏、横井秀基、笠原正登、森 潔、桒原孝成、今牧博貴、石井輝、古賀健一、森慶太、加藤有希子、大野祥子、菅原照、向山政志、中尾一和
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] Systemic Deletion of CTGF Ameliorates Anti-Glomerular Basement Membrane Nephritis with Reduction of Macrophage Infiltration (2013)
  • Author(s): N.Toda, H.yokoi, M,Kasahara, K,Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, T.Matsusaka, K.Nakao, M.Mukoyama
  • Organizer: Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] Inducible CTGF (CCN2) Knockout Mice Attenuates Anti-Glomerular Basement Membrane Nephritis (2012)
  • Author(s): ③N.Toda, H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, M.Mukoyama, K.Nakao 2012年10月30日-11月4日
  • Organizer: 米国腎臓病学会年次総会
  • Place of Presentation: サンディエゴ、米国
• [Presentation] Inducible CTGF (CCN2) Knockout Mice Attenuates Anti-Glomerular Basement Membrane Nephritis (2012)
  • Author(s): N.Toda, H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, M.Mukoyama, K.Nakao
  • Organizer: American Society of Nephrology Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] Functional analysis of miR-30c, miR-26a and miR-379 in podocytes and their potential roles in diabetic nephropathy (2011)
  • Author(s): K.Koga, H.Yokoi, M.Mukoyama, K.Mori, M.Kasahara, T.Kuwabara, H.Imamaki, T.kawanishi, A.Ishii, K.P.Mori, Y.Kato, M.Saleem, A.Sugawara, K.Nakao
  • Organizer: 米国腎臓病学会年次総会
  • Place of Presentation: フィラデルフィア、米国
• [Presentation] Functional analysis of miR-30c, miR-26a and miR-379 in podocytes and their potential roles in diabetic nephropathy (2011)
  • Author(s): Koga K, Yokoi H, Mukoyama M, Mori K, Kasahara M, Kuwabara T, Imamaki H, Kawanishi T, Ishii A, Mori PK, Kato Y, Saleem M, Sugawara A, Nakao K
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, PA, USA
• [Remarks] 京都大学腎臓内科ホームページ
  • URL: http://www.kidney.kuhp.kyoto-u.ac.jp/research/yokoi.html
• [Remarks] 京都大学大学院医学研究科内科学講座 内分泌代謝内科
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html
• [Remarks] webページ
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html