The role of NHE3 (Slc9a3) in oxalate and sodium transport by mouse intestine and regulation by cAMP

Stephens, Christine E.; Whittamore, Jonathan M.; Hatch, Marguerite

doi:10.14814/phy2.14828

Cited by 3 publications

(1 citation statement)

References 91 publications

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“…3 F ). While Nhe3 has been reported to regulate sodium levels in mouse ileal tissue ( Murtazina et al, 2011 ), more recent observations indicate that Nhe3 plays a modest role in sodium fluxes in the distal ileum ( Stephens et al, 2021 ). Therefore, there could be additional mechanisms by which sodium levels are maintained in the ileum.…”

Section: Discussionmentioning

confidence: 99%

Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C

Mishra

Bose

Kiran

et al. 2021

Journal of Experimental Medicine

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Activating mutations in receptor guanylyl cyclase C (GC-C), the target of gastrointestinal peptide hormones guanylin and uroguanylin, and bacterial heat-stable enterotoxins cause early-onset diarrhea and chronic inflammatory bowel disease (IBD). GC-C regulates ion and fluid secretion in the gut via cGMP production and activation of cGMP-dependent protein kinase II. We characterize a novel mouse model harboring an activating mutation in Gucy2c equivalent to that seen in an affected Norwegian family. Mutant mice demonstrated elevated intestinal cGMP levels and enhanced fecal water and sodium content. Basal and linaclotide-mediated small intestinal transit was higher in mutant mice, and they were more susceptible to DSS-induced colitis. Fecal microbiome and gene expression analyses of colonic tissue revealed dysbiosis, up-regulation of IFN-stimulated genes, and misregulation of genes associated with human IBD and animal models of colitis. This novel mouse model thus provides molecular insights into the multiple roles of intestinal epithelial cell cGMP, which culminate in dysbiosis and the induction of inflammation in the gut.

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Section: Discussionmentioning

confidence: 99%