title: Protective effect of 1,25-dihydroxyvitamin D3 on ethanol-induced intestinal barrier injury both in vitro and in vivo.
abstract: Studies have suggested the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in protecting intestinal barrier function from injuries induced by multiple reagents. Vitamin D deficiency was reported to be associated with poor prognosis in patients with alcoholic liver disease (ALD). This study is designed to investigate the effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms utilizing Caco-2 cell monolayers and a mouse model with acute ethanol injury. In Caco-2 monolayers, ethanol significantly increased monolayer permeability, disrupted TJ distribution, increased phosphorylation level of MLC, and induced generation of ROS compared with controls. However, pre-treatment with 1,25(OH)2D3 greatly ameliorated the ethanol-induced barrier dysfunction, TJ disruption, phosphorylation level of MLC, and generation of ROS compared with ethanol-exposed monolayers. Mice fed with vitamin d-sufficient diet had a higher plasma level of 25(OH)D3 and were more resistant to ethanol-induced acute intestinal barrier injury compared with the vitamin d-deficient group. These results suggest that the suppression of generation of ROS and increased phosphorylation level of MLC might be one of the mechanisms underlying the protective effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier injury and provide evidence for the application of vitamin D as therapeutic factors against ethanol-induced gut leakiness.
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Shan-Wen
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Animal Experiment Center, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Zi-Yi
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Chen
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Pan
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China.
authors.forename: Yu-Cun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, PR China. Electronic address: wangpengyuan2014@126.com.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018994:Myosin Light Chains / Q000378:metabolism; D010539:Permeability; D010766:Phosphorylation; D020011:Protective Agents / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000032:analysis
chemical_list: D018994:Myosin Light Chains; D020011:Protective Agents; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D000431:Ethanol; D002117:Calcitriol
keywords: 1,25(OH)(2)D(3); Ethanol; MLC; Reactive oxygen species (ROS); TEER; Tight junction