title: 1,25-Dihydroxyvitamin D3 preserves intestinal epithelial barrier function from TNF-α induced injury via suppression of NF-kB p65 mediated MLCK-P-MLC signaling pathway.
abstract: Substantial studies have demonstrated the protective effect of 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) on intestinal barrier function, but the mechanisms are not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TNF-α induced barrier dysfunction was further investigated in Caco-2 cell monolayers. The barrier function of Caco-2 monolayers was evaluated by measuring trans-epithelial electrical resistance (TEER) and FITC-Dextran 40,000 Da (FD-40) trans-membrane flux. ZO-1 and Occludin were chosen as markers of the localization of tight junction (TJ) proteins for immunofluorescence. The expression of MLCK and phosphorylation level of myosin light chain (MLC) were measured by immunoblotting. The activation of NF-kB p65 was analyzed by EMSA and immunofluorescence. The results suggest that 1,25(OH)2D3 preserves intestinal epithelial barrier function from TNF-α induced injury via suppression of NF-kB p65 mediated activation of MLCK-P-MLC signaling pathway.
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Shanwen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of 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, People's Republic of China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Chen
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of 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, People's Republic of China.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Yucun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China. Electronic address: wangpengyuan2014@126.com.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology*; D017931:DNA Primers; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D017931:DNA Primers; D018994:Myosin Light Chains; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009219:Myosin-Light-Chain Kinase; D002117:Calcitriol
keywords: 1,25(OH)2D3; MLCK; TNF-α; Tight junction (TJ); Trans-epithelial electrical resistance (TEER)