Identification of novel zinc-responsive protein and clarification of significance in colorectal cancer prevention
| Project/Area Number |
16K16281
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Eating habits
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| Research Institution | Ishikawa Prefectural University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 亜鉛 / 大腸炎 / マクロファージ / リンパ球 / Th17 / 大腸がん / 炎症性腸疾患 |
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| Outline of Final Research Achievements |
Hypozincemia regarded as a risk for colon cancer and colitis. However, the precise mechanisms involved in zinc deficiency of the intestinal inflammation remains unclear. This study demonstrates that zinc deficiency resulting from using a zinc chelator administration aggravates colonic inflammation through the activation of type 17 helper T (Th17) cells in mice. Flow cytometric analysis revealed that zinc deficiency significantly increases the proportion of pro-inflammatory (M1) macrophages in inflamed colon. A zinc chelator up-regulates IL-23p19 expression, which is deeply associated with Th17 development, in mouse bone marrow-derived macrophages (BMDMs). Furthermore, the nuclear accumulation of interferon-regulatory factor 5 is critically involved in IL-23p19 induction in zinc-deficient BMDMs. Thus, zinc deficiency aggravates colonic inflammation through activation of the IL-23/Th17 axis, and the activation is controlled by subcellular distribution of interferon-regulatory factor 5.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Secreted protein acidic and rich in cysteine functions in colitis via IL17A regulation in mucosal CD4(+) T cells.2018
Author(s)
Tanaka M, Takagi T, Naito Y, Uchiyama K, Hotta Y, Toyokawa Y, Ushiroda C, Hirai Y, Aoi W, Higashimura Y, Mizushima K, Okayama T, Katada K, Kamada K, Ishikawa T, Handa O, Itoh Y.
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Journal Title
J Gastroenterol Hepatol.
Volume: 33
Issue: 3
Pages: 671-680
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Partially hydrolyzed guar gum enhances colonic epithelial wound healing via activation of RhoA and ERK1/2.2016
Author(s)
Horii Y, Uchiyama K, Toyokawa Y, Hotta Y, Tanaka M, Yasukawa Z, Tokunaga M, Okubo T, Mizushima K, Higashimura Y, Dohi O, Okayama T, Yoshida N, Katada K, Kamada K, Handa O, Ishikawa T, Takagi T, Konishi H, Naito Y, Itoh Y
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Journal Title
Food Funct.
Volume: 8(7)
Issue: 7
Pages: 3176-3183
DOI
Related Report
Peer Reviewed
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[Journal Article] Protective effect of agaro-oligosaccharides on gut dysbiosis and colon tumorigenesis in high-fat diet-fed mice2016
Author(s)
Higashimura Y, Naito Y, Takagi T, Uchiyama K, Mizushima K, Ushiroda C, Ohnogi H, Kudo Y, Yasui M, Inui S, Hisada T, Honda A, Matsuzaki Y, Yoshikawa T
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Journal Title
Am. J. Physiol. Gastrointest. Liver Physiol.
Volume: 310
Issue: 6
Pages: G367-G375
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Prevention of colitis by controlled oral drug delivery of carbon monoxide.2016
Author(s)
Steiger C, Uchiyama K, Takagi T, Mizushima K, Higashimura Y, Gutmann M, Hermann C, Botov S, Schmalz HG, Naito Y, Meinel L.
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Journal Title
J Control Release.
Volume: 239
Pages: 128-36
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Partially hydrolysed guar gum ameliorates murine intestinal inflammation in association with modulating luminal microbiota and SCFA.2016
Author(s)
Takagi T, Naito Y, Higashimura Y, Ushiroda C, Mizushima K, Ohashi Y, Yasukawa Z, Ozeki M, Tokunaga M, Okubo T, Katada K, Kamada K, Uchiyama K, Handa O, Itoh Y, Yoshikawa
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Journal Title
Br. J. Nutr.
Volume: 116(7)
Pages: 1199-1205
Related Report
Peer Reviewed
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