PUBLICATION
Epidermal growth factor suppresses intestinal epithelial cell shedding via a MAPK dependent pathway
- Authors
- Miguel, J.C., Maxwell, A.A., Hsieh, J.J., Harnisch, L.C., Al Alam, D., Polk, D.B., Lien, C.L., Watson, A.J., Frey, M.R.
- ID
- ZDB-PUB-160401-18
- Date
- 2017
- Source
- Journal of Cell Science 130(1): 90-96 (Journal)
- Registered Authors
- Lien, Ching-Ling (Ellen), Maxwell, Adrienne
- Keywords
- Intestinal epithelium, Inflammatory bowel disease, Epidermal growth factor receptor, EGFR, MAP kinases, MAPKs, Epithelial cell, Cell shedding
- MeSH Terms
-
- Animals
- Caspase Inhibitors/pharmacology
- Caspases/metabolism
- Dogs
- Epidermal Growth Factor/pharmacology*
- Epithelial Cells/drug effects
- Epithelial Cells/metabolism*
- Intestines/cytology*
- MAP Kinase Signaling System/drug effects*
- Madin Darby Canine Kidney Cells
- Mice
- Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors
- Mitogen-Activated Protein Kinase Kinases/metabolism
- Protein Kinase Inhibitors/pharmacology
- Zebrafish
- rho GTP-Binding Proteins/metabolism
- PubMed
- 27026527 Full text @ J. Cell Sci.
Citation
Miguel, J.C., Maxwell, A.A., Hsieh, J.J., Harnisch, L.C., Al Alam, D., Polk, D.B., Lien, C.L., Watson, A.J., Frey, M.R. (2017) Epidermal growth factor suppresses intestinal epithelial cell shedding via a MAPK dependent pathway. Journal of Cell Science. 130(1):90-96.
Abstract
Cell shedding from the intestinal villus is a key element of tissue turnover, essential to maintain health and homeostasis. However, the signals regulating this process are not well understood. We asked whether shedding is controlled by epidermal growth factor receptor (EGFR), an important driver of intestinal growth and differentiation. In 3D ileal enteroid culture and cell culture models (MDCK, IEC-6, IPEC-J2 cells), extrusion events were suppressed by EGF, as determined by direct counting of released cells or rhodamine-phalloidin labeling of condensed actin rings. Blockade of MEK/ERK, but not other downstream pathways such as PI3K or PKC, reversed EGF inhibition of shedding. These effects were not due to a change in cell viability. Furthermore, EGF-driven MAPK signaling inhibited both caspase-independent and -dependent shedding pathways. Similar results were foundin vivo,in a novel zebrafish model for intestinal epithelial shedding. Together, the data show that EGF suppresses cell shedding in the intestinal epithelium through a selective, MAPK dependent pathway affecting multiple extrusion mechanisms. EGFR signaling may be a therapeutic target for disorders featuring excessive cell turnover, such as inflammatory bowel diseases.
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
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