Objective: Sulphate (SO42-) is an abundant component of intestinal mucins and its content is decreased in certain gastrointestinal diseases, including inflammatory bowel disease. In this study, we used the hyposulphataemic NaS1 sulphate transporter null (Nas1-/-) mice to investigate the physiological consequences of disturbed sulphate homeostasis on (i) intestinal sulfomucin content and mRNA expression, (ii) intestinal permeability and proliferation, (iii) dextran sulphate sodium (DSS) induced colitis and (iv) intestinal barrier function against the bacterial pathogen, Campylobacter jejuni.
Design: Intestinal sulphomucins and sialomucins were detected by high iron diamine staining, permeability was assessed by FITC-dextran uptake and proliferation was assessed by BrdU incorporation. Nas1-/- and wildtype (Nas1+/+) mice received DSS in drinking water and intestinal damage was assessed by histological, clinical and haematological measurements. Mice were orally inoculated with C. jejuni and intestinal and systemic infection was assessed. Ileal mRNA expression profiles of Nas1-/- and Nas1+/+ mice were determined by cDNA microarrays and validated by quantitative real time PCR.
Results: Nas1-/- mice exhibited reduced intestinal sulphomucin content, enhanced intestinal permeability and DSS-induced colitis, and developed systemic infections when challenged orally with C. jejuni. The transcriptional profile of 41 genes was altered in Nas1-/- mice, with the most up-regulated gene being pancreatic lipase-related protein 2 and most down-regulated gene being carbonic anhydrase-1 (Car1).
Conclusion: Sulphate homeostasis is essential for maintaining a normal intestinal metabolic state and hyposulphataemia leads to reduced intestinal sulphomucin content, enhanced susceptibility to toxin-induced colitis and impaired intestinal barrier to bacterial infection.
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