Vasoactive intestinal peptide upregulates MUC2 intestinal mucin via CREB/ATF1
| Autor: | Young Sam Kim, Soichiro Miura, Hwa Young Lee, Ryota Hokari, Suzanne C. Crawley, James R. Gum, Stacey C. Yang |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Physiology G protein Vasoactive intestinal peptide Mucin 2 Biology CREB digestive system p38 Mitogen-Activated Protein Kinases Cell Line Physiology (medical) Internal medicine medicine Cyclic AMP Humans Phosphorylation Protein kinase A Cyclic AMP Response Element-Binding Protein Extracellular Signal-Regulated MAP Kinases Promoter Regions Genetic G protein-coupled receptor Activating Transcription Factor 1 Mucin-2 Hepatology Mucin Gastroenterology Mucins Molecular biology Cyclic AMP-Dependent Protein Kinases digestive system diseases Up-Regulation Endocrinology biology.protein Signal transduction Signal Transduction Vasoactive Intestinal Peptide |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 289(5) |
| ISSN: | 0193-1857 |
| Popis: | VIP exerts a spectrum of effects as a potent anti-inflammatory factor. In addition, VIP increases expression of MUC2, a major intestinal secretory mucin. We therefore investigated the effects of VIP on the promoter activity of the 5′-flanking region of the MUC2 gene. VIP activated MUC2 transcription in human colonic epithelial cells via cAMP signaling to ERK and p38. cAMP/Epac/Rap1/B-Raf signaling was not involved in MUC2 reporter activation. Furthermore, activation of MUC2 transcription was independent of many of the reported downstream effectors of G protein-coupled receptors, such as PKC, Ras, Raf, Src, calcium, and phosphoinositide 3-kinase. VIP induced cAMP response element-binding protein (CREB)/ATF1 phosphorylation, and this was prevented by treatment with inhibitors of either MEK or p38 and by PKA and MSK1 inhibitor H89. CREB/ATF1 and c-Jun were shown to bind to an oligonucleotide encompassing a distal, conserved CREB/AP1 site in the 5′-flanking region of the MUC2 gene, and this cis element was shown to mediate promoter reporter activation by VIP. This study has identified a new, functional cis element within the MUC2 promoter and also a new pathway regulating MUC2 expression, thus providing further insight into the molecular mechanism of VIP action in the colon. These findings are relevant to the normal biology of the colonic mucosa as well as to the development of VIP as a therapeutic agent for treatment of inflammatory bowel disease. |
| Databáze: | OpenAIRE |
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