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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 | Human cardiovascular responses to a 60-min bath at 40 degrees C显示文摘 | MIWA C MATSUKAWA T | 1994 | Environ Med1994，38，1： | 1 |
| 3 | Skin sympathetic neuroeffector response is attenuated dose-dependently by systemic prostaglandin E1 injection in humans显示文摘 | Iwase S Yamamoto K Miwa C | 2000 | NeurosciLett2000，292，3： | 1 |
| 4 | Pulmonary mocosa associated lymphoid tissue (MALT) lymphoma inSjOgren' s syndrome showing only the LIP pattern radiologieally显示文摘 | WATANABE Y KOYAMA S MIWA C | 2012 | Intern Med2012，51，5： | 1 |
| 5 | Epidemic of hand, foot and mouth disease in Gifu Prefecture in 1978显示文摘 | Miwa C Ohtani M Watanabe H | 1980 | Jpn J Med Sci Biol1980，33，3： | 1 |
| 6 | Serum thioredoxin and al- pha-tocopherol concentrations in patients with major risk factors 显示文摘 | Miwa K Kishimoto C Nakamura H | 2005 | Circulation Journal2005，69，3： | 1 |
| 7 | Positional cloning and characterization of a paired box and homeobox-containing gene from the aniridia region显示文摘 | Ton C C Hirvonen H Miwa H | 1991 | Cell1991，67，： | 1 |
| 8 | Human cardiovascular responses to a 60-min bath at 40 degrees C显示文摘 | Miwa C Matsukawa T Iwase S | 1994 | Environ Med1994，38，1： | 1 |
| 9 | Complement promotes the development of inflammatory T-helper 17 cells through synergistic interaction with Tol-like receptor signaling and interleukin-6 production显示文摘 | Fang C Zhang X Miwa T | 2009 | {H}Blood2009，，05： | 1 |
| 10 | Vibsane-type diterpenes from Taiwannse Viburnum odoratissirmum显示文摘 | Miwa K Ih Sheng C Yoshiyasu F | 2001 | Chem Pharm Bull2001，49，： | 1 |
| 11 | Mammalian target of ra- pamycin:a central node of complex signaling caseades显示文摘 | Dobashi Y Watanabe Y Miwa C | 2011 | Int J Clin Exp Pathol2011，4，5： | 1 |
| 12 | Isolation and Characterization of Mierosatellite Loci From the Japanese Red Pine, Pinus densiflora 显示文摘 | LIAN C MIWA M HOGETSU T | 2000 | Molecular Ecology2000，9，8： | 1 |
| 13 | Cardiovascular function in the elderly during water immersion显示文摘 | Sugiyama Y Miwa C Xue YX | 1993 | Environ Med1993，37，1： | 1 |
| 14 | Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins显示文摘 | Martin D Brand Charles Affourtit Telma C Esteves Katherine Green Adrian J Lambert Satomi Miwa Julian L Pakay Nadeene Parker | 2004 | Free Radical Biology and Medicine2004，，6： | 1 |
| 15 | Gravity effect on the electrie field deposition of two-dimensional particle arrays显示文摘 | Dushkin C Miwa T Nagayama K | 1998 | Chem Phys Lett1998，285，34： | 1 |
| 16 | Named entity recognition with multiple segment representations显示文摘 | Cho H C Okazaki N Miwa M | 2013 | Information Processing&Management2013，49，4： | 1 |
| 17 | Outcrossing and paternity analysis of pi-nus densiflora by microsatellite polymorphism显示文摘 | LIAN C MIWA M HOGETSU T | 2001 | Heredity2001，87，： | 1 |
| 18 | Mito-chondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2显示文摘 | Gavriilidis C Miwa S yon Zglinieki T | 2013 | Arthritis Rheum2013，65，2： | 1 |
| 19 | Study of photo-assisted electrochemical degradation of carbaryl at dimensionally stable anodes 显示文摘 | MALPASS G R P MIMA D W MIWA A C P | 2009 | J Hazard Mater2009，，10： | 1 |
| 20 | Effects of fuel cetane number and aromatics on combustion process and emissions of a direct-injection diesel engine显示文摘 | KIDOGUCHI Y YANG C KATO R MIWA K | 2000 | JSAE Review2000，21，4： | 1 |
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