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Novel therapeutic strategy for liver regeneration focusing on local TGF-beta activation mechanism

Research Project

Project/Area Number 24791434
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

HAYASHI Hiromitsu  熊本大学, 大学院生命科学研究部, 助教 (80625773)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsTGF-β / トロンボスポンディン / 肝再生 / TSP-1 / TGF-beta / トロンボスポンディン1
Research Abstract

We performed 70% hepatectomy in mice receiving normal saline, LSKL peptide, and sham operation.LSKL peptide was administered intraperitoneally at abdominal closure and 6 h after hepatectomy. Perioperative plasma TSP-1 levels were measured by ELISA system in patients with hepatectomy. LSKL peptide administration attenuated Smad2 phosphorylation at 6h. S-phase entry of hepatocytes was accelerated at 24 and 48h by LSKL peptide administration, and which resulted in faster recovery of the residual liver and body weight. H&E staining and blood biochemical examinations revealed no significant adverse effects occurred following the two LSKL peptide administrations. LSKL peptide during the early period after hepatectomy can promote liver regeneration. The transient inhibition of TSP-1/TGF-beta signal activation using LSKL peptide in the early period after hepatectomy may thus be a promising strategy to promote liver regeneration following hepatectomy.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (10 results)

  • [Journal Article] Percentage of future liver remnant volume before portal vein embolization influences the degree of liver regeneration after hepatectomy. J Gastrointest Surg2013

    • Author(s)
      Okabe H, Beppu T, Nakagawa S, Yoshida M, Hayashi H, Masuda T, Imai K, Mima K, Kuroki H, Nitta H, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Yamashita Y, Baba H.
    • Journal Title

      J Gastrointest Surg

      Volume: 17(8) Issue: 8 Pages: 1447-51

    • DOI

      10.1007/s11605-013-2237-y

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thrombospondin-1 is a novel negative regulator of liver regeneration after partial hepatectomy through transforming growth factor-beta1 activation in mice2012

    • Author(s)
      Hayashi H, Sakai K, Baba H, Sakai T
    • Journal Title

      Hepatology

      Volume: 55(5) Issue: 5 Pages: 1562-73

    • DOI

      10.1002/hep.24800

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma2012

    • Author(s)
      Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, Watanabe M, Beppu T, Tamada M, Nagano O, Saya H, Baba H
    • Journal Title

      Cancer Res

      Volume: 1;72(13) Pages: 3414-23

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biological Significance of Local TGF-β Activation in Liver Diseases2012

    • Author(s)
      Hayashi H, Sakai T
    • Journal Title

      Front Physiol

      Volume: 6;3 Pages: 12-12

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] External biliary drainage and liver regeneration after major hepatectomy.2012

    • Author(s)
      太田尾 龍、岡部 弘尚、他
    • Journal Title

      British Journal of Surgery

      Volume: 99 Issue: 11 Pages: 1569-1574

    • DOI

      10.1002/bjs.8906

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biological significance of latent TGF-βactivation in liver.2012

    • Author(s)
      林 洋光
    • Journal Title

      Frontiers in Physiology

      Volume: 3 Pages: 12-12

    • DOI

      10.3389/fphys.2012.00012

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 肝再生抑制因子トロンボスポンディン1 に対する阻害ペプチドを用いた肝再生促進療法2014

    • Author(s)
      林 洋光
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ(東京都)
    • Year and Date
      2014-05-29
    • Related Report
      2013 Final Research Report
  • [Presentation] LSKL peptide inhibits thrombospondin-1- mediated TGF-β signal activation and accelerates liver regeneration after hepatectomy in mice2014

    • Author(s)
      Kuroki H, Hayashi H, Nakagawa S, Sakamoto K, Higashi T, Nitta H, Hashimoto D, Chikamoto A, Beppu T, Baba H
    • Organizer
      AACR Annual Meeting 2014
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2014-04-07
    • Related Report
      2013 Final Research Report
  • [Presentation] Integrin beta6 はTGF-beta による上皮間葉転換を促進し肝内胆管癌の進展に関与する2014

    • Author(s)
      東 孝暁, 林 洋光, 黒木 秀幸, 中川 茂樹, 坂本 慶太, 横山 奈穂美, 新田 英利, 近本亮, 別府 透, 馬場 秀夫
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-04-03
    • Related Report
      2013 Final Research Report
  • [Presentation] TSP-1 を介したTGF-β活性化による肝再生抑制機構をターゲットとした新規肝再生促進療法の開発2014

    • Author(s)
      黒木 秀幸, 林 洋光, 中川 茂樹, 東 孝暁, 橋本 大輔, 阿部 真也, 新田 英利, 近本 亮, 石河 隆敏, 別府 透, 馬場 秀夫
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-04-03
    • Related Report
      2013 Final Research Report
  • [Presentation] TGF-β活性化による肝再生抑制機構の解明と活性化阻害peptide を用いた肝再生促進療法開発2013

    • Author(s)
      林 洋光, 黒木 秀幸, 美馬 浩介, 中川 茂樹, 新田 英利, 今井 克憲, 蔵元 一崇, 近本 亮, 別府 透, 馬場 秀夫
    • Organizer
      第25回日本肝胆膵外科学会学術集会
    • Place of Presentation
      ホテル東日本宇都宮(栃木県)
    • Year and Date
      2013-06-12
    • Related Report
      2013 Final Research Report
  • [Presentation] TGF β活性化機構による肝再生抑制機構の解明と新戦略の構築2013

    • Author(s)
      林 洋光, 黒木 秀幸, 美馬 浩介, 中川 茂樹, 新田 英利, 今井 克憲, 蔵元 一崇, 近本 亮, 別府 透, 酒井 尚雄, 馬場 秀夫
    • Organizer
      第113回日本外科学会学術集会
    • Place of Presentation
      マリンメッセ福岡
    • Year and Date
      2013-04-11
    • Related Report
      2013 Final Research Report
  • [Presentation] TGF β 活性化機構による肝再生抑制機構の解明と新戦略の構築2013

    • Author(s)
      林洋光、黒木秀幸、美馬浩介 、中川茂樹 、新田英利 、今井克憲 、蔵元一崇 、近本 亮 、別府 透 、酒井尚雄、馬場秀夫
    • Organizer
      第113回日本外科学会
    • Place of Presentation
      マリンメッセ福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] TGF-β活性化による肝再生抑制機構の解明と活性化阻害peptideを用いた肝再生促進療法開発2013

    • Author(s)
      林洋光、黒木秀幸、美馬浩介、中川茂樹、新田英利、今井克憲、蔵元一崇、近本 亮、別府 透、馬場秀夫
    • Organizer
      第25回日本肝胆膵外科学会・学術集会
    • Place of Presentation
      ホテル東日本宇都宮
    • Related Report
      2013 Annual Research Report
  • [Presentation] 肝再生抑制機構の解明と新規標的トロンボスポンディン1 の同定2012

    • Author(s)
      林 洋光
    • Organizer
      第112回日本外科学会学術集会
    • Place of Presentation
      幕張メッセ国際会議場(千葉県)
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝再生抑制機構の解明と新規標的トロンボスポンディン1の同定2012

    • Author(s)
      林 洋光
    • Organizer
      第112回日本外科学会定期学術集会
    • Place of Presentation
      千葉 幕張メッセ国際会議場
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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