Epigenetic regulation through estrogen and its receptors in inflammatory bowel disease model

2020 Fiscal Year Annual Research Report

• Project/Area Number: 19K16477
• Research Institution: University of Miyazaki
• Principal Investigator: チョウジョウフ ナランツオツク 宮崎大学, 医学部, 講師 (90640962)
• Project Period (FY): 2019-04-01 – 2021-03-31
• 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.

Research Products

• [Journal Article] Essential role of submandibular lymph node dendritic cells in protective sublingual immunotherapy against murine allergy (2020)
  • 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
  • Journal Title: Communications Biology Volume: 3 Pages: 742
  • DOI: 10.1038/s42003-020-01466-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Photodynamic therapy using a novel phosphorus tetraphenylporphyrin induces anticancer effect via Bax/Bcl-xL-related mitochondrial apoptosis in biliary cancer cells (2020)
  • Author(s): Mai NNH, Yamaguchi Y, Choijookhuu N, Matsumoto J, Nanashima A, Takagi H, Sato K, Tuan LQ, Hishikawa Y
  • Journal Title: Acta Histochem Cytochem Volume: 53 Pages: 61-72
  • DOI: 10.1267/ahc.20-00002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pivotal role of CD103 in the development of psoriasiform dermatitis (2020)
  • 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
  • Journal Title: Scientific Reports Volume: 10 Pages: 8371
  • DOI: 10.1038/s41598-020-65355-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New tropisms of porcine epidemic diarrhoea virus (PEDV) in pigs naturally coinfected by variants bearing large deletions in the spike (S) protein and PEDVs possessing an intact S protein (2020)
  • Author(s): Diep NV, Choijookhuu N, Ozawa M, Fuke N, Hishikawa Y, Yamaguchi R
  • Journal Title: Transboundary and Emerging Diseases Volume: 67 Pages: 2589-2601
  • DOI: 10.1111/tbed.13607
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The advanced detection system using fluorescence resonance energy transfer based molecular beacon probe for in situ hybridization (2020)
  • Author(s): Choijookhuu N, Ishizuka T, Shibata Y, Xu Y, Koji T, Hishikawa Y
  • Organizer: 第61回日本組織細胞化学
• [Presentation] Photodynamic therapy by a novel porphyrin induces mitochondrial apoptosis (2020)
  • Author(s): Mai NNH, Yamaguchi Y, Choijookhuu N, Matsumoto J, Nanashima A, Takagi H, Sato K, Hishikawa Y
  • Organizer: 第52日本臨床分子形態学会
• [Presentation] Hmgb2 Regulates The Differentiation Of Mesenchymal Stem Cells By Suppressing The Expression Of β-catenin (2020)
  • Author(s): Yokoe T, Lee D, Chosa E, Taniguchi N, Choijookhuu N, Hishikawa Y
  • Organizer: Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research
• [Remarks] 宮崎大学医学部 解剖学講座組織細胞化学分野
  • URL: http://www.med.miyazaki-u.ac.jp/home/anatomy1