2020 Fiscal Year Annual Research Report
Epigenetic regulation through estrogen and its receptors in inflammatory bowel disease model
Project/Area Number |
19K16477
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Research Institution | University of Miyazaki |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Keywords | Epigenetics / Estrogen receptor / GPR30 / IBD |
Outline of Annual Research Achievements |
For the investigation of the estrogen signaling mechanism in colon, we examined the expression of c-Jun. Immunohistochemistry in mouse colonic mirror sections were revealed the ERβ and c-Jun were co-localized in same cells, that indicates ERb is acting through AP-1 sites in colonic epithelium. In our study, we first confirmed that ERβ dominance in colonic tissue, but not ERα. Southwestern histochemistry was detected highly similar co-localization of ERE-binding proteins with ERβ indicated that ERβ is functionally active in colon. Next, to investigate epigenetic treatment approach is useful in colitis model, we examined the effects of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA) in 1.5% dextran sulfate sodium (DSS) induced colitis model. Pro-inflammatory cytokines IL-6, TNF-α, Ccl2 gene expression peaked on day 5 in DSS-treated mouse colon, whereas SAHA+DSS treatment significantly decreased proinflammatory gene expressions. Moreover, we found GPR30 expression in mouse colonic epithelium, which mediates estrogen action in non-genomic pathway. GPR30 expression was significantly decreased in DSS-treated mice. In addition, the localization of CD11b showed that migratory inflammatory cells were dramatically decreased by SAHA treatment. Thus, we conclude that the HDAC inhibitor, SAHA, attenuates inflammatory changes in DSS induced colitis by suppressing local secretion of pro-inflammatory cytokines and chemokines. Altogether these results indicate that epigenetic treatment have an anti-inflammatory effects through estrogen signaling.
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Research Products
(8 results)
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[Journal Article] Essential role of submandibular lymph node dendritic cells in protective sublingual immunotherapy against murine allergy2020
Author(s)
Miyanaga N, Takagi H, Uto T, Fukaya T, Nasu J, Fukui T, Nishikawa Y, Sparwasser T, Choijookhuu N, Hishikawa Y, Nakamura T, Tono T, Sato K
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Journal Title
Communications Biology
Volume: 3
Pages: 742
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pivotal role of CD103 in the development of psoriasiform dermatitis2020
Author(s)
Fukui T, Fukaya T, Uto T, Takagi H, Nasu J, Miyanaga N, Nishikawa Y, Koseki H, Choijookhuu N, Hishikawa Y, Yamashita Y, Sato K
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Journal Title
Scientific Reports
Volume: 10
Pages: 8371
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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