Evaluation of novel biomarkers in peritoneal fibrosis

• Project/Area Number: 22590910
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: KASAHARA Masato 京都大学, 医学研究科, 准教授 (50393351)
• Co-Investigator(Kenkyū-buntansha): MORI Kiyoshi 京都大学, 大学院・医学研究科, 准教授 (60343232)
• Co-Investigator(Renkei-kenkyūsha): YOKOI Hideki 京都大学, 大学院・医学研究科, 助教 (90378779)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腹膜透析 / 腹膜中皮細胞 / ノックアウトマウス / 腹膜炎 / pleiotrophin / 線維化 / 炎症 / 腹膜線維症 / Ngal / EPS / バイオマーカー / Pleiotrophin

Research Abstract

We used PTN knockout mice to evaluate the role of pleiotrophin (PTN) in peritoneal fibrosis, and measured the concentration of PTN in the peritoneal effluents from peritonealdialysis patients. We also measured the concentration of Ngal in peritoneal effluents.1. Role PTN in peritoneal fibrosis using PTN knockout micePTN mRNA in the peritoneum of peritoneal fibrosis mice was gradually increased. PTN knockout mice with peritoneal fibrosis model reduced inflammatory cell migration and cytokines and peritoneal permeability compared with control mice2. Measurement of PTN in peritoneal effluents and PTN mRNA in peritoneal tissues.We could detect PTN in peritoneal effluents and showed increase of PTN in effluents from patients with peritonitis. 3. Measurement of Ngal in peritoneal effluentsNgal concentration in peritoneal effluents from patients with bacterial peritonitis was 10 times higher than that from control patients. Ngal score (adjusted by internal control) was high in patients receiving PD more than 100 months.

Research Products

• [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] Intra-abdominal fat area is a predictor for new onset of individual components of metabolic syndrome: MEtabolic syndRome and abdominaL ObesiTy (MERLOT study) (2012)
  • Author(s): Nakao YM, Miyawaki T, Yasuno S, Nakao K, Tanaka S, Ida M, Hirata M, Kasahara M, Hosoda K, Ueshima K, Nakao K
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci Volume: 88:454-461
  • NAID: 130001924760
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491080/
• [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] Effects of renin-angiotensin system blockades on cardiovascular outcomes in patients with diabetes mellitus: A systematic review and meta-analysis (2012)
  • Author(s): Nakao YM, Teramukai S, Tanaka S, Yasuno S, Fujimoto A, Kasahara M, Ueshima K, Nakao K, Hinotsu S, Nakao K, Kawakami K
  • Journal Title: Diabetes Res Clin Pract Volume: 96(1):68-75 Issue: 1 Pages: 68-75
  • DOI: 10.1016/j.diabres.2011.11.025
• [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] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice.Nephrol Dial Transplant (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 Volume: 25:2120-2124 Issue: 7 Pages: 2120-2124
  • DOI: 10.1093/ndt/gfq029
• [Journal Article] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice (2010)
  • Author(s): Yokoi H., Kasahara M., Mori K, 他9名
  • Journal Title: Nephrol Dial Transplant Volume: 25 Pages: 2120-2124
  • Peer Reviewed
• [Presentation] Analyses of microRNAs targeting CTGF in peritoneal fibrosis mouse model (2012)
  • Author(s): K.Koga, M.Mukoyama, H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, H.Imamaki, T.Kawanishi, A.Ishii, K.P.Mori, Y.Kato, S.Ono, N.Toda, A.Sugawara, K.Nakao
  • Organizer: American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-11-02
• [Presentation] pleiotrophinの腹膜線維症における意義と発現 (2011)
  • Author(s): 横井秀基、笠原正登、森潔、小川喜久、桑原孝成、今牧博貴、川西智子、古賀健一、石井輝、戸田尚宏、大野祥子、村松喬、村松壽子、菅原照、向山政志、中尾一和
  • Organizer: 第17回日本腹膜透析医学会学術集会・総会
  • Place of Presentation: さいたま
  • Year and Date: 2011-09-24
• [Presentation] Pleiotrophin causes peritoneal inflammation and mesothelial cell proliferation in a mouse model of peritoneal fibrosis (2011)
  • Author(s): H.Yokoi, M.Kasahara, M.Mukoyama, K.Mori, Y.Ogawa, T.Kuwabara, H.Imamaki, T.kawanishi, K.Koga, A.Ishii, Y.Kato, K.P.Mori, H.Muramatsu, T.Muramatsu, A.Sugawara, K.Nakao
  • Organizer: World Congress of nephrology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2011-04-11
• [Presentation] Pleiotrophin causes peritoneal inflammation and mesothelial cell proliferation in a mouse model of peritoneal fibrosis (2011)
  • Author(s): Yokoi H, Kasahara M, Mori K, Ogawa Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Kato Y, Mori PK、 Toda N, Ohno S, Muramatsu H, Muramatsu T, Sugawara A,Mukoyama M, Nakao K
  • Organizer: World Congress of nephrology
  • Place of Presentation: Vancouver, BC, Canada
  • Year and Date: 2011-04-11
• [Presentation] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice (2010)
  • Author(s): Yokoi H., Kasahara M., Mori K, 他6名
  • Organizer: 米国腎臓学会学術集会
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2010-11-19
• [Presentation] The role of 3,4-dideoxyglucosone-3-ene inperitoneal fibrosis (2010)
  • Author(s): H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, R.Yamada, S.Namoto, T.Yamamoto, N.Seki, T.Yamaguchi, N.Souma, A.Sugawara, M.Mukoyama, K.Nakao
  • Organizer: American Society of Nephrology
  • Place of Presentation: Denver, US
  • Year and Date: 2010-11-18
• [Presentation] Atrial natriuretic peptide prevents peritoneal adhesion formation with inhibiting macrophage and CD3-positive cell infiltration (2010)
  • Author(s): H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, T.kawanishi, K.Koga, A.Ishii, K.Mori, Y.Kato, A.Sugawara, M.Mukoyama, K.Nakao
  • Organizer: American Society of Nephrology
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-11-18
• [Presentation] Analyses of microRNAs Targeting CTGF in Peritoneal Fibrosis Mouse Model
  • Author(s): Koga Kenichi
  • Organizer: American Society of Nephrology
  • Place of Presentation: San Diego, USA
• [Remarks] 京都大学大学院医学研究科内分泌代謝内科ホームページ
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.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]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html
• [Patent(Industrial Property Rights)] 腹膜癒着防止用医薬組成物 (2011)
  • Inventor(s): 中尾一和、横井秀基、向山政志、笠原正登、森潔、古谷真優美
  • Industrial Property Rights Holder: 国立大学法人京都大学、第一三共株式会社
  • Acquisition Date: 2011-10-20