Elucidation of mechanism and suppression system of Thioredoxin in colitis-associated cancer

• Project/Area Number: 24791407
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: TORII Mie 三重大学, 医学(系)研究科(研究院), リサーチアソシエイト (60615285)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: チオレドキシン / 大腸炎 / 大腸がん / MIF / サイトカイン

Research Abstract

In this study, we examined the role of an antioxidative protein, thioredoxin (TRX), in colon inflammation and promotion of colitis-associated cancer. To study the role of TRX in the carcinogenesis process, we used a mouse model of azoxymethane- and dexstran sodium salt-induced colitis and colitis-associated cancer in WT and TRX-Tg mouse. We found that TRX-Tg mice developed less colon tumors but accelerated growth of emerging colon tumors. RT-PCR analysis of colon tissues and mesenteric lymph nodes isolated at various time points revealed that mRNAs for inflammatory cytokines and chemokines other than MIF were downregulated, whereas the expression of MIF mRNA was upregulated in TRX-Tg mice at all time points tested. Collectively, these results suggest that TRX suppresses the development of colon cancers possibly due to the downregulation of the production of inflammatory cytokines involved in tumorgenesis, while promotes growth of emerging cancer through upregulated MIF production.

Research Products

• [Journal Article] Effect of cold ischemia/reperfusion injury and/or shear stress with portal hypertension on the expression of matrix metalloproteinase-9 (2012)
  • Author(s): Hori T, Uemoto S, Chen F, Ann-Baine MT, Gardner LB, Hata T, Kuribayashi K, Kato T, Saito K, Wang L, Torii M, Endo K, Jobara K, Sulistiono B, Nguyen JH
  • Journal Title: Ann Gastroenterol Volume: 25 (4) Pages: 345-351
  • Peer Reviewed