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Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals
- Source :
- American journal of physiology. Gastrointestinal and liver physiology. 292(1)
- Publication Year :
- 2006
-
Abstract
- Epimorphin is a mesenchymal protein that regulates morphogenesis of epithelial cells. Our preliminary study suggested a novel function of epimorphin in enhancing survival of intestinal epithelial cells (IEC). Oxidative stress leads to cell injury and death and is suggested to be a key contributor to pathogenesis of inflammatory bowel disease. This study was conducted to determine whether epimorphin protects IEC from oxidative stress. Rat intestinal epithelial cell line IEC-6 was cultured with epimorphin (10 and 20 μg/ml), and the life span of IEC was assessed. The mean life span of IEC-6 cells was prolonged 1.9-fold ( P < 0.0006) by treatment with epimorphin. We then examined the epimorphin signaling pathways. Epimorphin phosphorylated epidermal growth factor (EGF) receptor, activated the MEK/extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and phosphatidylinositol 3 (PI3) kinase/Akt pathways, phosphorylated Bad, and induced Bcl-XL and survivin. Hydrogen peroxide (1 mM) induced cell death in 92% of IEC-6 cells, but epimorphin dramatically diminished (88.7%) cell death induced by hydrogen peroxide ( P < 0.0001). This protective effect of epimorphin was significantly attenuated by inhibitors of MEK and PI3 kinase ( P < 0.0001) or EGF receptor-neutralizing antibody ( P = 0.0007). In wound assays, the number of migrated cells in the wound area decreased (72.5%) by treatment with 30 μM hydrogen peroxide, but epimorphin increased the number of migrated cells 3.18-fold ( P < 0.0001). These results support a novel function of epimorphin in protecting IEC from oxidative stress. This anti-oxidative function of epimorphin is dramatic and is likely mediated by the activation of EGF receptors and the MEK/extracellular signal-regulated kinase and PI3 kinase/Akt signaling pathways and through the induction of anti-apoptotic factors.
- Subjects :
- MAPK/ERK pathway
medicine.medical_specialty
Physiology
Cell Survival
Apoptosis
Biology
Cell Line
Phosphatidylinositol 3-Kinases
Epidermal growth factor
Physiology (medical)
Internal medicine
medicine
Animals
Intestinal Mucosa
Receptor
Protein kinase B
Membrane Glycoproteins
Hepatology
Kinase
Gastroenterology
MAP Kinase Kinase Kinases
Epithelium
Cell biology
Rats
Enzyme Activation
ErbB Receptors
Oxidative Stress
Endocrinology
medicine.anatomical_structure
Cell culture
Signal transduction
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 01931857
- Volume :
- 292
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Accession number :
- edsair.doi.dedup.....cef32f93312bea074a9e955cffd16e42