Evaluation of novel biomarkers in peritoneal fibrosis

2012 Fiscal Year Final Research Report

• 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
• Keywords: 腹膜透析 / 腹膜中皮細胞 / ノックアウトマウス / 腹膜炎

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: Perit Dial Int Volume: 33:143-154
  • DOI: doi:10.3747/pdi.2011.00033
• [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
  • 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
  • DOI: doi:10.1681/ASN.2011100985
• [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
  • DOI: doi:10.1007/s00125-012-2578-1
• [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
  • DOI: 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, Kasahara M, Mori K, Ogawa Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Kato Y, Mori KP, Toda N, Ohno S, Muramatsu H, Muramatsu T, Sugawara A, Mukoyama M, Nakao K
  • Journal Title: Kidney Int Volume: 81:160-169
  • DOI: doi:10.1038/ki.2011.305
• [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
  • DOI: doi:10.1093/ndt/gfq029
• [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 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] 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
• [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
• [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
  • Industrial Property Number: 特許公開 2011-207867
  • Acquisition Date: 2011-10-20