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

Jennifer Miguel, Adrienne Maxwell, Jonathon Hsieh, Lukas Harnisch, Denise Al Alam, Brent Polk, Ching-Ling Lien, Alastair Watson, Mark R. Frey

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26 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)90-96
Number of pages7
JournalJournal of Cell Science
Volume130
Issue number1
Early online date29 Mar 2016
DOIs
Publication statusPublished - 2 Jan 2017

Keywords

  • intestine
  • EGF
  • apoptosis

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