Plasmin inhibition protects against dextran sulfate sodium-induced colitis

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791501
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Juntendo University
• Principal Investigator: KOMIYAMA Hiromitsu 順天堂大学, 医学部, 講師 (30348982)
• Research Collaborator: HATTORI Koichi 東京大学, 医科学研究所, 特任准教授 (10360116)
• Project Period (FY): 2011 – 2012
• Keywords: 炎症性腸疾患 / マトリックスメタロプロテアーゼ / TNFα / 線維素溶解系 / 炎症性サイトカイン / 潰瘍性大腸炎 / クローン病

Research Abstract

Treatment of ulcerative colitis is generally effective in relieving symptoms, but is not curative. Typically, this disease evolves with a relapsing and remitting course. Tissue remodeling by proteases like matrix metalloproteinases (MMP) have been described as a component of inflammatory bowel disease. There is mounting evidence that MMPs are the predominant proteinases expressed in the gut mucosa during active ulcerative colitis. Others and we showed that plasmin can activate several MMPs.Here, we investigated the function of MMP9 and plasminogen in a DSS (Dextran sulfate sodium) induced animal model of acute colitis. Pharmacological inhibition, an active -center-directed inhibitor or targeted gene deletion of Plg or MMP9 prevented increased morbidity of wildtype mice during DSS colitis. This was associated with a reduced inflammatory cell infiltration in colon tissues and correlated with impaired colonic cytokine level elevation. In summary, our data show that the absence of Plg and MMP9 strongly inhibits the inflammatory response in acute colitis, which is associated with alleviation of the course of the disease.

Research Products

• [Journal Article] Investigation of peripheral blood free cancer cells using CEA mRNA in perioperative colorectal cancer patients (2013)
  • Author(s): Kiichi Nagayasu, Hiromitsu Komiyama, Shun Ishiyama, Dai Ogura, Rina Takahashi, Yoshihiko Tashiro, Koichiro Niwa, Kiichi Sugimoto, Yutaka Kojima, Michitoshi Goto, Yuichi Tomiki, Shinichiro Niwa, Kazuhiro Sakamoto
  • Journal Title: Molecular and Clinical Oncology Volume: 1(4) Pages: 668-674
  • Peer Reviewed
• [Journal Article] Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice (2012)
  • Author(s): Tashiro Y, Nishida C, Sato-Kusubata K, Ohki-Koizumi M, Ishihara M, Sato A, Gritli I, Komiyama H, Sato Y, Dan T, Miyata T, Okumura K, Tomiki Y, Sakamoto K, Nakauchi H, Heissig B, Hattori K.
  • Journal Title: Blood Volume: 119(26) Pages: 6382-93
  • Peer Reviewed
• [Journal Article] Analysis of the Effects of Alleviating Adverse Events and Improving Completion in Colorectal Cancer Patients with Postoperative Adjuvant Chemotherapy with PSK (2012)
  • Author(s): Kiichi Sigimoto, Rina Takahashi, Shun Ishiyama, Masaki Hata, Hirohiko Kamiyama, Hiromitsu Komiyama (corresponding author), Makoto Takahashi, Yutaka Kojima, Michitoshi Goto, Hironobu Sengoku, Yuichi Tomiki, Kazuhiro Sakamoto
  • Journal Title: Juntendo Medical Journal Volume: 58(5) Pages: 422-430
• [Journal Article] Glasgow Prognostic Score (GPS) as a prognostic factor in patients undergoing curative surgery forcolorectal cancer (2012)
  • Author(s): Sugimoto K, Komiyama H, Kojima Y, Goto M,Tomiki Y, Sakamoto K.
  • Journal Title: Dig Surg Volume: 29(6) Pages: 503-509
• [Journal Article] 生体内組織再生における線維素溶解系因子 PAI-1 の機能解明 (2011)
  • Author(s): 田代 良彦, 西田知恵美, イスマイル・グリツリ , 小泉摩季子, 佐藤 弥生, 小見山 博光, 佐藤亜紀, 坂本 一博, 宮田 敏男, 楠畑 かおり, 中内 啓光, ハイジッヒ・ベアテ , 服部 浩一
  • Journal Title: 臨床血液(0485-1439) Volume: 52巻 9 号 Pages: 1136
• [Remarks] ホームページ
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/index.html