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Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium
Author(s) -
Miyoshi Hiroyuki,
VanDussen Kelli L,
Malvin Nicole P,
Ryu Stacy H,
Wang Yi,
Sonnek Naomi M,
Lai ChinWen,
Stappenbeck Thaddeus S
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694660
Subject(s) - biology , prostaglandin e2 , epithelium , intestinal epithelium , microbiology and biotechnology , endocrinology , genetics
Adaptive cellular responses are often required during wound repair. Following disruption of the intestinal epithelium, wound‐associated epithelial ( WAE ) cells form the initial barrier over the wound. Our goal was to determine the critical factor that promotes WAE cell differentiation. Using an adaptation of our in vitro primary epithelial cell culture system, we found that prostaglandin E2 ( PGE 2 ) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to in vivo WAE cells. WAE cell differentiation was a permanent state and dominant over enterocyte differentiation in plasticity experiments. WAE cell differentiation was triggered by nuclear β‐catenin signaling independent of canonical Wnt signaling. Creation of WAE cells via the PGE 2 ‐Ptger4 pathway was required in vivo , as mice with loss of Ptger4 in the intestinal epithelium did not produce WAE cells and exhibited impaired wound repair. Our results demonstrate a mechanism by which WAE cells are formed by PGE 2 and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury.