Role of Transient Receptor Potential Vanilloid 4 activation in indomethacin-induced intestinal damage.

Role of Transient Receptor Potential Vanilloid 4 activation in indomethacin-induced intestinal damage.
Am J Physiol Gastrointest Liver Physiol. 2014 May 1;
Authors: Yamawaki H, Mihara H, Suzuki N, Nishizono H, Uchida K, Watanabe S, Tominaga M, Sugiyama T
Abstract
Gastrointestinal ulcers and bleeding are serious complications of non-steroidal anti-inflammatory drug (NSAID) use. While administration of antibiotics and Toll-like receptor 4 knockdown mitigate NSAID-induced enteropathy, the molecular mechanism of these effects is poorly understood. Intestinal hyperpermeability is speculated to trigger the initial damage due to NSAID use. Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel expressed throughout the gastrointestinal (GI) tract epithelium, which is activated by temperature, extension, and chemicals such as 5,6-epoxyeicosatrienoic acid (5,6-EET). The aim of this study was to investigate the possible role of TRPV4 in NSAID-induced intestinal damage. TRPV4 mRNA and protein expression were confirmed by RT-PCR and immunochemistry, respectively, in mouse and human tissues while TRPV4 channel activity of the intestinal cell line IEC-6 was assessed by Ca(2+)-imaging analysis. TRPV4 activators or the NSAID indomethacin significantly decreased transepithelial resistance (TER) in IEC-6 cells, and indomethacin-induced TER decreases were inhibited by specific TRPV4 inhibitors or siRNA TRPV4 knockdown, as wel...

Source: Am J Physiol Gastroi... - May 1, 2014 Category: Gastroenterology Authors: Yamawaki H, Mihara H, Suzuki N, Nishizono H, Uchida K, Watanabe S, Tominaga M, Sugiyama T Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research