Epidermal growth factor suppresses intestinal epithelial cell shedding both in vitro and in vivo via a MAPK dependent pathway

Miguel, Jennifer, Maxwell, Adrienne, Hsieh, Jonathon, Harnisch, Lukas, Alam, Denise Al, Polk, Brent, Lien, Ching-Ling, Watson, Alastair ORCID: https://orcid.org/0000-0003-3326-0426 and Frey, Mark R. (2017) Epidermal growth factor suppresses intestinal epithelial cell shedding both in vitro and in vivo via a MAPK dependent pathway. Journal of Cell Science, 130 (1). pp. 90-96. ISSN 0021-9533

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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 found in 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.

Item Type:	Article
Additional Information:	© 2017. Published by The Company of Biologists Ltd http://www.biologists.com/user-licence-1-1/
Uncontrolled Keywords:	intestine,egf,apoptosis
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	Pure Connector
Date Deposited:	01 Apr 2016 10:11
Last Modified:	21 Aug 2023 01:00
URI:	https://ueaeprints.uea.ac.uk/id/eprint/58037
DOI:	10.1242/jcs.182584

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