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WNT1‐inducible protein 1 functions as a pro‐repair molecule in the intestine
Author(s) -
Quiros Miguel,
Nishio Hikaru,
Neumann Philipp,
Leoni Giovanna,
Bernal Gabriela,
Feng Mingli,
Keshavarzian Ali,
Mutlu Ece,
Parkos Charles,
Nusrat Asma
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.142.10
Subject(s) - wound healing , wnt signaling pathway , downregulation and upregulation , microbiology and biotechnology , inflammation , cancer research , signal transduction , intestinal mucosa , immunology , chemistry , biology , medicine , biochemistry , gene
In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces. The epithelial reparative response is influenced by inflammation at sites of injury. Wnt‐b catenin signaling plays an important role in controlling intestinal epithelial homeostasis. We identified increased expression of a WNT1‐inducible signaling protein 1 (WISP1) in biopsy‐induced resealing intestinal mucosal wounds. WISP1 treatment of model intestinal epithelial cell (IEC) lines in vitro promotes wound repair by increasing epithelial cell proliferation. WISP1 associates with LRP6 and b1 integrin that are cell surface transmembrane proteins. Analysis of the signaling pathways revealed activation of src and Akt that promote epithelial cell proliferation and ultimately wound repair. In vivo analysis of healing intestinal mucosal wounds in response to biopsy‐induced injury demonstrated upregulation of WISP1 mRNA and protein in resealing intestinal mucosal wounds. Increased secretion of WISP1 in response to the anti‐inflammatory cytokine IL‐10 was observed in healing murine intestinal mucosal wounds. Lastly, WISP1 mRNA and protein was upregulated in human biopsies from patients with active inflammatory bowel disease. In summary, the above findings demonstrate an important role of WISP1 in promoting intestinal mucosal wound repair.