Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse

Objective: Sulfate (SO42-) is an abundant component intestinal mucins and its content is decreased in certain gastrointestinal diseases, including inflammatory bowel disease. In this study, the hyposulfataemic NaS1 transporter null (Nas1(-/-)) mice were used to the physiological consequences of disturbed sulfate homeostasis on (1) intestinal sulfomucin content and mRNA expression; (2) intestinal permeability and proliferation; (3) dextran sulfate sodium (DSS)-induced colitis; and (4) intestinal barrier function against the bacterial pathogen, Campylobacter jejuni. Methods: Intestinal sulfomucins and sialomucins were detected by high iron diamine staining, permeability assessed by fluorescein isothiocyanate (FITC)-dextran uptake, and proliferation was assessed by 5( BrdU) incorporation. Nas1(-/-) and wild-type (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 Nas1(-/-) and Nas1(+/+) mice were determined by cDNA microarrays and validated by quantitative real-time PCR. Results: Nas1(-/-) mice exhibited reduced intestinal sulfomucin content, enhanced intestinal permeability 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 most upregulated gene being pancreatic lipase-related protein 2 and the most downregulated gene being carbonic anhydrase 1 (Car1). Conclusion: Sulfate homeostasis is essential for maintaining a normal intestinal metabolic state, and hyposulfataemia leads to reduced intestinal sulfomucin content, enhanced susceptibility to toxin-induced colitis and impaired intestinal barrier to bacterial infection.