The effect of serine phosphorylated claudin-7 on the epithelial barrier and the modulation by transient receptor potential vanilloid 4 in human colonic cells

Publication date: December 2018Source: Biomedicine & Pharmacotherapy, Volume 108Author(s): Yuan-Yuan Huang, Zhen-Kai Wang, Jing Li, Su-Wen Bai, Bing Shen, Juan Du, Xian-Ming Xia, Fang-Yu WangAbstractAbnormal phosphorylation of claudins changes the interaction and aggregation of tight junction proteins, affecting the intestinal epithelial barrier. Selective blockade of transient receptor potential vanilloid 4 (TRPV4) alleviated experimental colitis. Whether TRPV4 affects the intestinal epithelial barrier and the relationship to claudin-7 phosphorylation remain unknown. In the present study, we investigated the TRPV4 expression in human colonic tissues and colonic cells. Using the site-directed mutagenesis approach, we also identified the roles of claudin-7 phosphorylation in the epithelial barrier and the relationship between TRPV4 and claudin-7 phosphorylation. Increased TRPV4 expression was found in the colonic mucosa from IBD patients. In colonic cells, the mutation of claudin-7 at position 204 decreased the TRPV4 expression. Mutation of claudin-7 at position 204 significantly decreased the FD20 permeability in monolayer colonic cells, while mutations of claudin-7 at positions S206 and S207 increased the FD20 permeability. Meanwhile, mutations of claudin-7 at positions S204 and S207 increased the TER in monolayer colonic cells. TRPV4 agonist GSK1016790 A increased the FD20 permeability in the control group, cld7-wild group, cld7-S206A group and cld7-S207 A group, while ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research