Role of microRNA targeting PTN and CTGF in peritoneal dialysis

• Project/Area Number: 25461246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nara Medical University (2015); Kyoto University (2013-2014)
• Principal Investigator: Kasahara Masato 奈良県立医科大学, 医学部, 病院教授 (50393351)
• Co-Investigator(Kenkyū-buntansha): YOKOI HIDEKI 京都大学, 医学研究科, 助教 (90378779)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腹膜透析 / microRNA / マウス / トランスフェクション / 培養細胞 / 内科 / 線維化

Outline of Final Research Achievements

microRNA regulates protein transcription of the targeted gene. We investigated the role of miRNA using peritoneal fibrosis mice induced by intraperitoneal injection of chlorhexidine gluconate (CG), and showed the increase of miR-26a and miR-30c both of which target CTGF and of miR-93 targeting VEGF. Administration of PDGF-BB or Angiotensin II induced miR-26a and miR-30c expression in cultured mesothelial cell line MeT5A. We further demonstrated the amelioration of peritoneal fibrosis induced by CG in tamoxifen-inducible systemic CTGF conditional knockout mice.

Research Products

• [Journal Article] MicroRNA-26a inhibits TGF-β-induced extracellular matrix expression in podocytes by targeting CTGF and is downregulated in diabetic nephropathy. (2015)
  • Author(s): Koga K, Yokoi H, Mori K, Kasahara K, Kuwabara T, Imamaki H, Ishii A, Mori KP, Kato Y, Ohno S, Toda N, Saleem MA, Sugawara A, Nakao K, Yanagita M, Mukoyama M.
  • Journal Title: Diabetologia Volume: 58 Issue: 9 Pages: 2169-80
  • DOI: 10.1007/s00125-015-3642-4
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [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, Ueshima K.
  • Journal Title: Clin Exp Nephrol Volume: in press
  • Peer Reviewed
• [Presentation] Deficiency of CTGF ameliorates peritoneal fibrosis in mice (2016)
  • Author(s): Naohiro Toda, Hideki Yokoi, Masato Kasahara, Kiyoshi Mori, Akira Ishii, Motoko Yanagita, Masashi Mukoyama
  • Organizer: 16th congress of international society of peritoneal dialysis
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-02-28
  • Int'l Joint Research / Invited
• [Presentation] 遺伝子改変動物を用いた腹膜線維化進展機序の解明 (2015)
  • Author(s): 横井秀基、戸田尚宏、笠原正登、柳田素子
  • Organizer: 第21回日本腹膜透析医学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2015-11-28
• [Presentation] Glomeular microRNA-26a expression correlates with eGFR in diabetic nephropathy and its regulation in podocytes (2014)
  • Author(s): Koga, Yokoi, Kasahara, Mori, Kuwabara, Imamaki, Sugawara, Matsusaka, Nakao, Yanagita, Mukoyama
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] microRNA-26a attenuates TGFbeta-induced extracellular matrix production by inhibiting CTGF and Smad2 in diabetic nephropathy (2013)
  • Author(s): K.Koga, M.Mukoyama, H.Yokoi, K.Mori, M.Kasahara, T.Kuwabara, H.Imamaki, A.Ishii, K.P.Mori, Y.Kato, S.Ono, N.Toda, Moin A. Saleem, A.Sugawara, K.Nakao
  • Organizer: World Congress of Nephrology WCN 2013
  • Place of Presentation: Hong Kong, China
• [Remarks] 京都大学大学院医学研究科腎臓内科学
  • URL: http://www.kidney.kuhp.kyoto-u.ac.jp/research/yokoi.html