Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse. Issue 7 (6th February 2009)

• Record Type: Journal Article
• Authors: Dawson, P A; Huxley, S; Gardiner, B; Tran, T; McAuley, J L; Grimmond, S; McGuckin, M A; Markovich, D
• Is Part Of: Gut. Volume 58:Issue 7(2009)
• Page Start: 910
• Page End: 919
• Publication Date: 2009-02-06
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2007.147595
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: Sulfate (SO4 2− ) is an abundant component of intestinal mucins and its content is decreased in certain gastrointestinal diseases, including inflammatory bowel disease. In this study, the hyposulfataemic NaS1 sulfate transporter null ( Nas1 −/− ) mice were used to investigate 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 was assessed by fluorescein isothiocyanate (FITC)–dextran uptake, and proliferation was assessed by 5-bromodeoxyuridine (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 of 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 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 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.