Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells.

Claudins, and particularly claudin-2, are important regulatory components of tight junction permeability. A better understanding of the involvement of claudin-2 in intestinal barrier functions requires the characterization of its distribution and regulation in the intestine. Interestingly, the claudin-2 gene promoter harbors a number of similarities to that of sucrase-isomaltase, a marker of enterocyte differentiation. We thus investigated the expression of claudin-2 in relation to the transcription factors CDX2, HNF-1alpha, and GATA-4 in the human intestine. The characterization of claudin-2 and the expression of the above transcription factors were performed by immunofluorescence, Western blot, and RT-PCR in the developing human intestinal epithelium. The functional role of CDX2, HNF-1alpha, and GATA-4 on claudin-2 regulation was also examined by ectopic expression studies in intestinal cell models. Claudin-2 was detected in both crypt and villus cells of the small intestine but restricted to undifferentiated crypt cells in the colon. CDX2 and HNF-1alpha were expressed along the entire intestine whereas GATA-4 was undetectable in the colon. Accordingly, in the colonic Caco-2 cell model, claudin-2 was found to be present only in undifferentiated cells. Like in the colonic epithelium, GATA-4 was found to be also lacking in Caco-2 cells while CDX2 and HNF-1alpha were present at significant levels. Cotransfection experiments showed that the claudin-2 promoter was activated by CDX2, HNF-1alpha, and GATA-4 in a cooperative manner. Furthermore, forced GATA-4 expression in Caco-2 cells enhances maintenance of claudin-2 expression during differentiation. These observations suggest that optimal claudin-2 expression in the gut relies on the presence of GATA-4, suggesting a role for this factor in intestinal regionalization.

Escaffit F ，Boudreau F ，Beaulieu JF 《JOURNAL OF CELLULAR PHYSIOLOGY》

Hepatocyte nuclear factor-1 alpha, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription. Implication for the developmental regulation of the sucrase-isomaltase gene.

Boudreau F ，Rings EH ，van Wering HM ，Kim RK ，Swain GP ，Krasinski SD ，Moffett J ，Grand RJ ，Suh ER ，Traber PG ... -  《JOURNAL OF BIOLOGICAL CHEMISTRY》

Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line.

Benoit YD ，Paré F ，Francoeur C ，Jean D ，Tremblay E ，Boudreau F ，Escaffit F ，Beaulieu JF ... -  《-》

Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha.

Sakaguchi T ，Gu X ，Golden HM ，Suh E ，Rhoads DB ，Reinecker HC ... -  《JOURNAL OF BIOLOGICAL CHEMISTRY》

The effect of cytostatic drug treatment on intestine-specific transcription factors Cdx2, GATA-4 and HNF-1alpha in mice.

de Koning BA ，Lindenbergh-Kortleve DJ ，Pieters R ，Rings EH ，Büller HA ，Renes IB ，Einerhand AW ... -  《CANCER CHEMOTHERAPY AND PHARMACOLOGY》