Expanding pathophysiological roles of the GC-C signalling axis in intestine based on animal models of human diseases
| Animal model | Target | Observations | Conclusion | Reference |
| Mice: GI function in the absence of GC-C expression | GC-C receptor | No diarrhoeal symptoms on exposure to STa Interestingly, no changes were found in the intestinal fluidity of GC-C knockout mice | GC-C is a necessary component of maintaining the intestinal barrier. However, further research is needed to determine the effects of guanylin peptides in knockout mice | 90 |
| Mice: colorectal transformation induced by high-fat diet | Guanylin–GUCY2C signalling axis | Caloric suppression led to decreased guanylin–GUCY2C activity and tumourigenesis | There is potential for using GC-C agonists in the prevention of colorectal cancer in obese patients | 16 |
| Mice: visceral hypersensitivity | Colorectal GC-C receptors | Downstream cGMP activation and exposure to stretch receptive endings decreased pain and hypersensitivity | GC-C agonists can relieve visceral hypersensitivity | 4 12 60 |
| Mice: visceral hypersensitivity | Colorectal GC-C receptors | Direct uroguanylin exposure to stretch receptive endings decreased pain and hypersensitivity | GC-C agonists can relieve visceral hypersensitivity | 12 |
| Mice: spontaneous colitis | GC-C receptors | On exposure to lipopolysaccharide, GC-C knockout mice experienced severe inflammation, possibly due to systemic cytokine burst of loss of mucosal immune cell immunosuppression | GC-C signalling plays an important role in intestinal inflammation and damage | 62 |
| Mice: microbiota | GC-C receptors | GC-C knock out mice had higher faecal bacterial loads. Decreased guanylin expression was noted in both knockout and control mice, with greater difference in knockout mice | GC-C signalling pathway contributes to host immune defence by reducing bacterial load and decreasing risk of systemic infection | 91 |
| Rats: zinc deficiency–induced diarrhoea | Uroguanylin | Zinc deficiency has been associated with increased mRNA expression of preprouroguanylin in the small intestine, colon, stomach, kidney, thymus and testis | Zinc deficiency could cause diarrhoea via the upregulation of uroguanylin | 92 |
| Mice: colon adenocarcinoma | Uroguanylin | Oral uroguanylin replacement therapy resulted in decreased intestinal polyp formation in the Min/+ mouse model for colorectal cancer | GC-C agonists are potential new targets in the prevention of intestinal polyps and cancers | 11 |
GC-C, guanylate cyclase-C.