Vitamin D3 induces vitamin D receptor and HDAC11 binding to relieve the promoter of the tight junction proteins
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Feng-Hua Liu1, Shan-Shan Li2,, Xiao-Xi Li 2,, Shuai Wang 2,3, Mao-Gang Li 2, Li Guan4, Tian-Gang Luan4, Zhi-Gang Liu2, Zhan-Ju Liu1 and Ping-Chang Yang2
1The Department of Gastroenterology, The Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072, China
2The Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen 518060, China
3Longgang ENT Hospital, Shenzhen ENT Institute, Shenzhen 518116, China
4Affiliated Luohu Hospital, Shenzhen University, Shenzhen 518001, China
Ping-Chang Yang, email: email@example.com
Zhan-Ju Liu, email: firstname.lastname@example.org
Keywords: intestine, epithelium, barrier function, vitamin D, histone deacetylase
Received: October 15, 2016 Accepted: April 12, 2017 Published: May 08, 2017
Intestinal epithelial barrier dysfunction and vitamin D (VitD)-deficiency play a critical role in a large number of diseases. The histone deacetylases (HDAC) are associated with a large number of immune diseases. This study tests a hypothesis that the interaction between VitD and HDAC is associated with the regulation of epithelial barrier functions. In this study, human intestinal epithelial cell line, T84 cells, was cultured into monolayers to be used as a model to test the epithelial barrier functions. We observed that in a VitD-deficient environment, the T84 monolayer barrier function was compromised. Exposure to calcitriol (the active form of VitD3) in the culture increased the expression of VitD receptor (VDR) in T84 cells. In a VitD-sufficient environment, VDR formed a complex with histone deacetylase-11 (HDAC11); the complex was markedly decreased in a VitD-deficient environment. We also observed that significantly more binding of HDAC11 to the promoter of the tight junction proteins inhibit the gene transcription activities of these loci in the VitD-deficient environment, which were abolished by the presence of calcitriol in the culture. In conclusion, the interaction between VDR and HDAC11 plays a crucial role in the maintenance of the epithelial barrier integrity.
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