scholarly journals Barrier dysfunction due to distinct defensin deficiencies in small intestinal and colonic Crohn's disease

2008 ◽  
Vol 1 (S1) ◽  
pp. S67-S74 ◽  
Author(s):  
J Wehkamp ◽  
M Koslowski ◽  
G Wang ◽  
E F Stange
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Barrier Dysfunction ◽  
Small Intestinal

TCF-1-mediated Wnt signaling regulates Paneth cell innate immune defense effectors HD-5 and -6: implications for Crohn's disease

2014 ◽  
Vol 307 (5) ◽  
pp. G487-G498 ◽  
Author(s):  
Julia Beisner ◽  
Zora Teltschik ◽  
Maureen J. Ostaff ◽  
Machteld M. Tiemessen ◽  
Frank J. T. Staal ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wnt Signaling ◽  
Paneth Cell ◽  
Immune Defense ◽  
Barrier Dysfunction ◽  
Mrna Isoforms ◽  
Stem Cell Maintenance ◽  
Small Intestinal

Wnt signaling regulates small intestinal stem cell maintenance and Paneth cell differentiation. In patients with ileal Crohn's disease (CD), a decrease of Paneth cell α-defensins has been observed that is partially caused by impaired TCF-4 and LRP6 function. Here we show reduced expression of the Wnt signaling effector TCF-1 (also known as TCF-7) in patients with ileal CD. Reporter gene assays and in vitro promoter binding analysis revealed that TCF-1 activates α-defensin HD-5 and HD-6 transcription in cooperation with β-catenin and that activation is mediated by three distinct TCF binding sites. EMSA analysis showed binding of TCF-1 to the respective motifs. In ileal CD patients, TCF-1 mRNA expression levels were significantly reduced. Moreover, we found specifically reduced expression of active TCF-1 mRNA isoforms. Tcf-1 knockout mice exhibited reduced cryptdin expression in the jejunum, which was not consistently seen at other small intestinal locations. Our data provide evidence that TCF-1-mediated Wnt signaling is disturbed in small intestinal CD, which might contribute to the observed barrier dysfunction in the disease.

scholarly journals Altered Expression of Laminins in Crohn's Disease Small Intestinal Mucosa

2000 ◽  
Vol 156 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Yamina Bouatrouss ◽  
F. Elizabeth Herring-Gillam ◽  
Jean Gosselin ◽  
Jacques Poisson ◽  
Jean-François Beaulieu
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Mucosa ◽  
Small Intestinal Mucosa ◽  
Altered Expression ◽  
Small Intestinal
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