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Protection of epithelial barrier function by the Crohn's disease associated gene protein tyrosine phosphatase n2
Michael Scharl1, Gisela Paul, Achim Weber
1Division of Gastroenterology, School of Medicine, University of California, San Diego, La Jolla, California 92093-0063, USA.
Gastroenterology
|October 13, 2009
Summary
Protein tyrosine phosphatase N2 (PTPN2) limits inflammation-induced intestinal barrier defects in Crohn's disease (CD). Reduced PTPN2 function exacerbates epithelial permeability, suggesting a role in CD pathogenesis.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Crohn's disease (CD) is linked to the PTPN2 gene, but its role in pathogenesis is unclear.
- Increased intestinal epithelial permeability is a key feature of CD.
- Understanding PTPN2's function is crucial for CD research.
Purpose of the Study:
- To investigate the role of Protein tyrosine phosphatase N2 (PTPN2) in the pathogenesis of Crohn's disease (CD).
- To determine how PTPN2 influences intestinal epithelial barrier function.
Main Methods:
- Utilized intestinal epithelial cell (IEC) lines (T84, HT29cl.19a) and primary patient samples.
- Employed Western blotting for protein analysis and small interfering RNA for PTPN2 knockdown.
- Assessed epithelial permeability and cytokine-induced signaling pathways.
Main Results:
- PTPN2 expression is elevated in CD intestinal tissues.
- Interferon-gamma (IFN-γ) increases PTPN2 expression and activity in IECs.
- PTPN2 knockdown enhances IFN-γ-induced STAT1/STAT3 phosphorylation and epithelial permeability, increasing claudin-2 expression.
Conclusions:
- PTPN2 activation by IFN-γ limits inflammatory signaling and barrier defects.
- PTPN2 plays a functional role in maintaining intestinal epithelial barrier integrity.
- These findings suggest PTPN2 is involved in Crohn's disease pathophysiology.
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