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| 1 | Disruption of the TWEAK/Fn14 pathway prevents 5-fluorouracil-induced diarrhea in mice显示文摘AIM To clarify the roles of TWEAK and its receptor Fn14 in 5-fluorouracil(5-FU)-induced diarrhea.METHODS Diarrhea was induced in wild-type(WT), Fn14 knockout(KO), and IL-13 receptor(IL-13R)α1 KO BALB/c mice using a single injection of 5-FU. Histological analysis, cytokine analysis, and flow cytometry was performed on ileal tissues and cells. Murine colon carcinomabearing mice were co-treated with an anti-TWEAK antibody and 5-FU. Embryonic fibroblast response to cytokines was also analyzed.RESULTS5-FU induced high Fn14 expression in epithelial cells. The severity of 5-FU-induced diarrhea was lower in Fn14 KO mice compared with WT mice. Administration of anti-TWEAK antibody reduced 5-FU-induced diarrhea without affecting the antitumor effects of 5-FU in vivo. 5-FU-induced expression of IL-13, IL-17 A, TNF-α, and IFN-γ in the ileum was Fn14 dependent. The severity of 5-FU-induced diarrhea was lower in IL-13Rα1 KO mice, indicating major role for IL-13 signaling via IL-13Rα1 in pathogenesis. We found that IL-13Rα2, an IL-13 neutralizing/cell protective receptor, was strongly induced by IL-33 in vitro and in vivo. IL-13Rα2 was upregulated in the ileum of 5-FU-treated Fn14 KO mice. Thus, the deletion of Fn14 upregulated IL-13Rα2 expression, which reduced IL-13 expression and activity. CONCLUSION Disruption of the TWEAK/Fn14 pathway affects several interconnected pathways, including those associated with IL-13, IL-33, and IL-13Rα2, to attenuate 5-FUinduced intestinal side effects. | Takuhito Sezaki Yuki Hirata Teruki Hagiwara Yuki I Kawamura Tadashi Okamura Rieko Takanashi Kenta Nakano Miwa Tamura-Nakano Linda C Burkly Taeko Dohi | 2017 | World Journal of Gastroenterology2017，23，13： | 3 |
| 2 | Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma显示文摘 | Kazunari Y Kenta I Koji S | 2003 | Int J Radiat Oncol Biol Phys2003，57，1： | 1 |
| 3 | Synthesis and antibacterial activity of novel fluoroalkylend-capped cooligomers containing dimethyl(octyl)-ammonium segments显示文摘 | HIDEO S KENTA Y YOSHIKO I | 2001 | European Polymer Journal2001，37，7： | 1 |
| 4 | Twin roll casting aluminum alloy strips显示文摘 | Haga T Kenta T Masaaki I | 2004 | J Mater Proc Tech2004，153，： | 1 |
| 5 | Twin roll casting aluminum alloy strips显示文摘 | HAGA T KENTA T MASAHIKO I | 2004 | J Mater Proc Tech2004，153，： | 1 |
| 6 | Twin roll casting of alumi- num alloy strips显示文摘 | TOSHIO H KENTA T MASAAKI I | 2004 | Journal of Materials Processing Technology2004，15，： | 1 |
| 7 | Piezoelectric properties of BNT based ceramics 显示文摘 | NOBORU I KENTA U | 1995 | Ferroelectrics1995，169，： | 1 |
| 8 | Imaging of highly oriented pyrolytic graphite corrosion accelerated by Pt particles显示文摘 | Zyun S Kenta I Kazuaki Y | 2005 | Electrochemistry Communications2005，7，11： | 1 |
| 9 | Imaging simulated smeared fingers with a sensor based on scattered-light detection显示文摘 | TAKESHI I KENTA K ICHIRO F | 2008 | Optical Review2008，15，3： | 1 |
| 10 | Twin roll casting of aluminum alloy strips 显示文摘 | Toshio H H Kenta T Masaaki I | 2004 | Mater Process Technol2004，153，10： | 1 |
| 11 | Piezoelectric properties of BNT based ceramics显示文摘 | NOBORU I KENTA U | 1995 | Ferroelectrics1995，169，： | 1 |
| 12 | 显示文摘 | Noboru I Kenta U | 1995 | Ferroelectrics1995，169，： | 1 |
| 13 | Low-dose candesartan cilexetil prevents early kidney damage in type 2 diabetic patients with mildly elevated blood pressure显示文摘 | Satoru M Tsutomu H Taro S Kenta O Reiko I Mitsuru A | 2003 | Hypertens Res2003，26，： | 1 |
| 14 | Prediction of subcellular locations of proteins: Where to proceed?显示文摘 | KENICHIRO I KENTA N | 2010 | Proteomics2010，，10： | 1 |
| 15 | Twin roll casting aluminum alloy strips显示文摘 | Haga T Kenta T Masaaki I | 2004 | J of Mater Proc Tech2004，153，： | 1 |
| 16 | Intracellular Iron Transport and Storage:From Molecular Mechanisms to Health Implications 显示文摘 | Elizabeth L Mackenzie Kenta I | 2008 | An- tioxid Redox Signal2008，10，6： | 1 |
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