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

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

  • Biomed Pharmacother. 2018 Dec;108:540-546. doi: 10.1016/j.biopha.2018.09.070.
Yuan-Yuan Huang 1 Zhen-Kai Wang 2 Jing Li 3 Su-Wen Bai 4 Bing Shen 4 Juan Du 4 Xian-Ming Xia 5 Fang-Yu Wang 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, the Fourth Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China.
  • 2 Department of Gastroenterology and Hepatology, Nanjing General Hospital of Nanjing Military Region, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing 210001, Jiangsu, China.
  • 3 Department of Gastroenterology and Hepatology, the Danyang People's Hospital, Danyang 212300, Jiangsu, China.
  • 4 Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, China.
  • 5 Department of Gastroenterology and Hepatology, the Fourth Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China. Electronic address: xiaxm@ahmu.edu.cn.
  • 6 Department of Gastroenterology and Hepatology, Nanjing General Hospital of Nanjing Military Region, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing 210001, Jiangsu, China. Electronic address: wangfy65@nju.edu.cn.
Abstract

Abnormal 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 the TRPV4 antagonist HC067047 decreased the FD20 permeability in the same groups. HC067047 treatment increased the TER in vector cells, cld7-wild cells and cld7-S206 A cells compared to the respective cells in GSK1016790A-treated groups. HC067047 treatment decreased the migration in vector cells, cld7-wild cells and cld7-S206 A cells compared to the respective cells in the GSK1016790A-treated groups. These results indicated that TRPV4 might be a target for the maintenance of the intestinal epithelial barrier and indicated the mechanism involved in the modulation of serine phosphorylated claudin-7.

Keywords

Claudin-7; Intestinal epithelial barrier; Phosphorylation; Transient receptor potential vanilloid 4.

Figures
Products