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Naringenin enhances intestinal barrier function through the expression and cytoskeletal association of tight junction proteins in C aco‐2 cells
Author(s) -
Noda Sakino,
Tanabe Soichi,
Suzuki Takuya
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300045
Subject(s) - occludin , naringenin , claudin , tight junction , microbiology and biotechnology , caco 2 , chemistry , heat shock protein , biology , biochemistry , cell , gene , flavonoid , antioxidant
Scope We have previously reported that naringenin promotes the tight junction ( TJ ) integrity in intestinal C aco‐2 cells. This study investigated the naringenin‐mediated effect in C aco‐2 cells with a particular focus on the modulation of TJ structure and claudin‐4 transcriptional regulation. Methods and results Naringenin (10∼100 μM) dose‐dependently enhanced TJ barrier integrity of C aco‐2 cells, indicated by transepithelial electrical resistance and FITC ‐dextran flux. Immunoblot analysis showed that naringenin increased the cytoskeletal association of TJ proteins, zonula occludens‐2, occludin, claudin‐1, and claudin‐4, simultaneously with increased occludin phosphorylation. The total expression of claudin‐4 was also increased by naringenin. Quantitative RT‐PCR and luciferase reporter assay revealed that naringenin transcriptionally increased the claudin‐4 expression with activation of claudin‐4 promoter. The mutation of the binding site of the transcriptional factor S p1 in the claudin‐4 promoter sequence and the pharmacological inhibition of S p1 partially suppressed the naringenin‐mediated activation of the claudin‐4 promoter. Further, naringenin induced the heat shock protein 70 expression in the cells. Conclusion Naringenin enhances barrier integrity through the assembly and expression of TJ proteins in intestinal epithelial cells. Naringenin‐mediated claudin‐4 expression occurs, at least partially, through S p1‐dependent transcriptional regulation. The induction of heat shock protein 70 may be also involved in the increased claudin‐4 expression.