Enhanced Expression of Transcription Factor GATA-4 in Inflammatory Bowel Disease and Its Possible Regulation by TGF-β1
| Autor: | Merja Ashorn, David B. Wilson, Leif C. Andersson, Hanna Haveri, Markku Heikinheimo, Sari Iltanen |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male TGF alpha Adolescent Cellular differentiation Immunology Apoptosis Smad Proteins Transforming Growth Factor beta1 Cell Line Tumor GATA6 Transcription Factor TGF beta signaling pathway Serum response factor Humans Immunology and Allergy Child Aged bcl-2-Associated X Protein Aged 80 and over biology Interleukin-6 Tumor Necrosis Factor-alpha Chemistry Transforming growth factor beta Middle Aged Inflammatory Bowel Diseases Intestinal epithelium GATA4 Transcription Factor Intestines Proto-Oncogene Proteins c-bcl-2 Transforming growth factor beta 3 Child Preschool Cancer research biology.protein Female Tumor necrosis factor alpha Signal Transduction |
| Zdroj: | Journal of Clinical Immunology. 29:444-453 |
| ISSN: | 1573-2592 0271-9142 |
| Popis: | Transforming growth factor beta 1 (TGF-beta1) promotes epithelial healing in inflammatory bowel disease. We hypothesized that GATA-4, a transcription factor cooperating with TGF-beta signaling pathway, is upregulated by TGF-beta1 in the inflamed intestinal epithelium.Normal and inflamed intestinal samples were subjected to immunohistochemistry for GATA-4/6 and the TGF-beta signaling pathway components Smad2/3/4. Proliferation and apoptosis were analyzed using Ki-67 and in situ DNA 3'-end labeling assays and Bax and Bcl-2 immunohistochemistry. Furthermore, GATA-4 was assessed in intestinal Caco-2 cells stimulated with TGF-beta1, or interleukin-6 and tumor necrosis factor alpha.GATA-4 was detected in only 20% of normal intestinal samples, but was upregulated in corresponding inflamed regions. GATA-6 expression remained unchanged during inflammation. TGF-beta1 and Smad3/4, but not Smad2, were expressed concomitantly with GATA-4 in inflamed bowel mucosa. In intestinal Caco-2 cells, TGF-beta1 upregulated GATA-4 and Smad2/3/4, whereas treatment with control cytokines had no effect. Inflammation was associated with increased epithelial cell apoptosis and the enhancement of Bcl-2, but not Bax.We surmise GATA-4 expression is upregulated in inflamed intestine correlating with the activation of TGF-beta signaling pathway. We speculate that TGF-beta1 drives GATA-4 expression during intestinal inflammation, these two components cooperating to promote epithelial healing. |
| Databáze: | OpenAIRE |
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