title: Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium.
abstract: 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 (PGE2) 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 PGE2-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 PGE2and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury.
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Hiroyuki
authors: H
authors: Miyoshi
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Kelli L
authors: 0000-0002-5810-0720
authors: KL
authors: VanDussen
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Nicole P
authors: NP
authors: Malvin
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Stacy H
authors: SH
authors: Ryu
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Yi
authors: Y
authors: Wang
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Naomi M
authors: NM
authors: Sonnek
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Chin-Wen
authors: CW
authors: Lai
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA stappenb@wustl.edu.
authors: Thaddeus S
authors: 0000-0002-6023-3901
authors: TS
authors: Stappenbeck
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015232:Dinoprostone / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D007413:Intestinal Mucosa / Q000293:injuries* / Q000502:physiology*; D051379:Mice; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: C545651:Ptger4 protein, mouse; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone
keywords: epithelium; prostaglandin; restitution; stem cell; wound repair