5,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cells

Defects in intestinal tight junction (TJ) barrier cause intestinal inflammation. We investigated the effects of 5,7-dimethoxyflavone (DMF), abundantly found in black ginger, on the TJ barrier in human intestinal Caco-2 cells. DMF reinforced TJ barrier integrity, indicated by increased transepithelia...

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Main Authors: Yunika Mayangsari, Mayu Okudaira, Chinatsu Mano, Yuki Tanaka, Osamu Ueda, Tomohiro Sakuta, Yoshiharu Suzuki, Yoshinari Yamamoto, Takuya Suzuki
Format: Article
Language:English
Published: Elsevier 2021-10-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1756464621002905
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author Yunika Mayangsari
Mayu Okudaira
Chinatsu Mano
Yuki Tanaka
Osamu Ueda
Tomohiro Sakuta
Yoshiharu Suzuki
Yoshinari Yamamoto
Takuya Suzuki
author_facet Yunika Mayangsari
Mayu Okudaira
Chinatsu Mano
Yuki Tanaka
Osamu Ueda
Tomohiro Sakuta
Yoshiharu Suzuki
Yoshinari Yamamoto
Takuya Suzuki
author_sort Yunika Mayangsari
collection DOAJ
description Defects in intestinal tight junction (TJ) barrier cause intestinal inflammation. We investigated the effects of 5,7-dimethoxyflavone (DMF), abundantly found in black ginger, on the TJ barrier in human intestinal Caco-2 cells. DMF reinforced TJ barrier integrity, indicated by increased transepithelial electrical resistance and reduced dextran permeability in Caco-2 cells. Immunoblot analysis revealed that the increases in the barrier-forming TJ molecules occludin and claudin-1 and the decrease in pore-forming claudin-2 in the cytoskeletal fraction of the cells were responsible for the TJ regulation. Increased occludin expression was sensitive to cycloheximide (an inhibitor of protein translation) and rapamycin (mechanistic target of rapamycin [mTOR] inhibitor). DMF reduced Cldn2 mRNA levels without suppressing its transcriptional activity; the reduction was associated with the upregulation of miR-16-5p. Thus, DMF-mediated reinforcement of intestinal TJ barrier was partly involved in the induction of occludin protein translation via mTOR and silencing Cldn2 mRNA via miR-16-5p.
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spelling doaj.art-3cdef59286f1465d899a5ee4fa65f77c2022-12-21T18:28:43ZengElsevierJournal of Functional Foods1756-46462021-10-01851046415,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cellsYunika Mayangsari0Mayu Okudaira1Chinatsu Mano2Yuki Tanaka3Osamu Ueda4Tomohiro Sakuta5Yoshiharu Suzuki6Yoshinari Yamamoto7Takuya Suzuki8Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan; Faculty of Agricultural Technology, Gadjah Mada University, Jl. Flora No 1, Depok, Sleman, Yogyakarta 55281, IndonesiaGraduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, JapanShiseido Global Innovation Center. 1-2-11 Takashima, Nishi-ku, Yokohama 220-0011, JapanShiseido Global Innovation Center. 1-2-11 Takashima, Nishi-ku, Yokohama 220-0011, JapanShiseido Global Innovation Center. 1-2-11 Takashima, Nishi-ku, Yokohama 220-0011, JapanShiseido Global Innovation Center. 1-2-11 Takashima, Nishi-ku, Yokohama 220-0011, JapanShiseido Global Innovation Center. 1-2-11 Takashima, Nishi-ku, Yokohama 220-0011, JapanGraduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, JapanGraduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan; Graduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan; Corresponding author at: Graduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan.Defects in intestinal tight junction (TJ) barrier cause intestinal inflammation. We investigated the effects of 5,7-dimethoxyflavone (DMF), abundantly found in black ginger, on the TJ barrier in human intestinal Caco-2 cells. DMF reinforced TJ barrier integrity, indicated by increased transepithelial electrical resistance and reduced dextran permeability in Caco-2 cells. Immunoblot analysis revealed that the increases in the barrier-forming TJ molecules occludin and claudin-1 and the decrease in pore-forming claudin-2 in the cytoskeletal fraction of the cells were responsible for the TJ regulation. Increased occludin expression was sensitive to cycloheximide (an inhibitor of protein translation) and rapamycin (mechanistic target of rapamycin [mTOR] inhibitor). DMF reduced Cldn2 mRNA levels without suppressing its transcriptional activity; the reduction was associated with the upregulation of miR-16-5p. Thus, DMF-mediated reinforcement of intestinal TJ barrier was partly involved in the induction of occludin protein translation via mTOR and silencing Cldn2 mRNA via miR-16-5p.http://www.sciencedirect.com/science/article/pii/S1756464621002905ClaudinDimethoxyflavonemicroRNAOccludinTight junction
spellingShingle Yunika Mayangsari
Mayu Okudaira
Chinatsu Mano
Yuki Tanaka
Osamu Ueda
Tomohiro Sakuta
Yoshiharu Suzuki
Yoshinari Yamamoto
Takuya Suzuki
5,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cells
Journal of Functional Foods
Claudin
Dimethoxyflavone
microRNA
Occludin
Tight junction
title 5,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cells
title_full 5,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cells
title_fullStr 5,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cells
title_full_unstemmed 5,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cells
title_short 5,7-Dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin-2 in human intestinal Caco-2 cells
title_sort 5 7 dimethoxyflavone enhances barrier function by increasing occludin and reducing claudin 2 in human intestinal caco 2 cells
topic Claudin
Dimethoxyflavone
microRNA
Occludin
Tight junction
url http://www.sciencedirect.com/science/article/pii/S1756464621002905
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