Article Text

PDF
Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse
  1. P A Dawson1,
  2. S Huxley1,
  3. B Gardiner2,
  4. T Tran3,
  5. J L McAuley3,
  6. S Grimmond2,
  7. M A McGuckin3,
  8. D Markovich1
  1. 1
    School of Biomedical Sciences, University of Queensland, St Lucia, Australia
  2. 2
    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
  3. 3
    Mucosal Diseases Program, Mater Medical Research Institute, Mater Hospital, South Brisbane, Australia
  1. Professor D Markovich, University of Queensland, St Lucia, QLD 4072, Australia; d.markovich{at}uq.edu.au

Abstract

Objective: Sulfate (SO42−) 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.

Statistics from Altmetric.com

Footnotes

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Digest
    Robin Spiller Severine Vermeire