Abstract
Guanylate cyclase-C (GC-C) is a multifunctional receptor encoded by the GUCY2C gene, representing an attractive target for therapy in several gastrointestinal diseases in humans. Little is known about this system in horses. We investigated for the first time the gene expression of guanylin, uroguanylin and GC-C receptors in different horse’s gastrointestinal tracts. Tissue samples from stomach, duodenum, jejunum, ileum, head and body of cecum, left and right dorsal colon, left and right ventral colon, pelvic flexure, transverse colon, descending colon and rectum were collected from adult horses within 1 h post mortem. For each sample, total RNA was extracted from 100 mg of ground tissue, and qRT-PCR performed on GUCA2a, GUCA2b and GUCY2 transcripts on a CFX96 Touch instrument. Data analysis was carried out with Bio-Rad CFX Manager software, and genes of interest normalized relative to the abundance of the two reference genes (SDHA, HPRT). Additionally, the protein expression levels of GC-C receptor were analyzed through western blotting. A common pattern of expression throughout the gastrointestinal lumen for all three investigated transcripts was found. The expression of GUCA2a, GUCA2b and GUCY2 genes was higher in jejunum, ileum, descending colon and rectum. The levels of expression of GC-C protein confirmed these data. The findings of this study might open new scenarios for the therapeutic approach to enteric diseases of horse using selective agonists of GC-C.
Highlights
Guanylin and uroguanylin are endogenous hormones involved in intestinal fluid homeostasis and bowel function of the gastrointestinal tract in several species; these hormones activate the guanylate cyclase-C (GC-C), a type I transmembrane receptor essentially expressed on the apical surface of intestinal epithelial cells
The activation of the Guanylate cyclase-C (GC-C)/cGMP pathway via guanylin and uroguanylin has been well established in various species; this pathway was shown to be essential in the restoration of mucosal barrier function during intestinal disorders, and the administration of synthetic agonists of this cascade can have beneficial effects
In the present study we found high expression of both mRNAs of GUCA2A and GUCA2B, with uroguanylin generally displaying higher levels with respect to guanylin
Summary
Guanylin and uroguanylin are endogenous hormones involved in intestinal fluid homeostasis and bowel function of the gastrointestinal tract in several species; these hormones activate the guanylate cyclase-C (GC-C), a type I transmembrane receptor essentially expressed on the apical surface of intestinal epithelial cells. The increase of intracellular concentrations of the GMPc second messenger triggers a signaling cascade that causes an uncontrolled release of electrolytes and water into the intestinal lumen, resulting in Guanylin, Uroguanylin and GC-C in Horses secretory diarrhea (Brierley, 2012). Its transcript is mainly expressed on epithelial cells of the gastrointestinal tract and was at first identified as the receptor for the bacterial heatstable enterotoxin (STa), produced by several enteric pathogens and responsible for the traveler’s diarrhea (Lin et al, 2010; Uranga et al, 2018)
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