{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T03:15:21Z","timestamp":1774149321555,"version":"3.50.1"},"reference-count":48,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:p>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 \u03b1-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 \u03b1-defensin HD-5 and HD-6 transcription in cooperation with \u03b2-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.<\/jats:p>","DOI":"10.1152\/ajpgi.00347.2013","type":"journal-article","created":{"date-parts":[[2014,7,4]],"date-time":"2014-07-04T05:57:55Z","timestamp":1404453475000},"page":"G487-G498","source":"Crossref","is-referenced-by-count":43,"title":["TCF-1-mediated Wnt signaling regulates Paneth cell innate immune defense effectors HD-5 and -6: implications for Crohn's disease"],"prefix":"10.1152","volume":"307","author":[{"given":"Julia","family":"Beisner","sequence":"first","affiliation":[{"name":"Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zora","family":"Teltschik","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen J.","family":"Ostaff","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Machteld M.","family":"Tiemessen","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J. 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