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http://purl.uniprot.org/citations/22465430http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22465430http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22465430http://www.w3.org/2000/01/rdf-schema#comment"

Background & aims

Prostaglandin-endoperoxide synthase (Ptgs)2 is an enzyme involved in prostaglandin production during the response to mucosal damage. Its expression is regulated, in part, by messenger RNA (mRNA)-binding proteins that control the stability of Ptgs2 mRNA. We used a precise system of colonic injury and repair to identify Ptgs2 mRNA-binding proteins.

Methods

We used endoscopy-guided mucosal excision to create focal injury sites in colons of mice. Wound beds from wild-type, Ptgs2(-/-), Ptgs2(+/-), and Myd88(-/-) mice were analyzed at 2-day intervals after injury for aspects of repair and Ptgs2 expression. We used cultured colonic mesenchymal stem cells (cMSCs) that express Ptgs2 to identify and analyze molecules that regulate Ptgs2 expression.

Results

Ptgs2(-/-) mice had defects in wound repair, validating the biopsy technique as a system to study the regulation of Ptgs2. Ptgs2(+/-) mice had similar defects in wound healing, so full induction of Ptgs2 is required for wound repair. In wild-type mice, levels of Ptgs2 mRNA increased significantly in the wound bed 2 and 4 days after injury; the highest levels of Ptgs2 were observed in cMSCs. In a functional short hairpin RNA knockdown screen, we identified Igf2bp1, a VICKZ (Vg1 RNA binding protein, Insulin-like growth factor II mRNA binding protein 1, Coding region determinant-binding protein, KH domain containing protein overexpressed in cancer, and Zipcode-binding protein-1) mRNA-binding protein, as a regulator of Ptgs2 expression in cMSCs. Igf2bp1 also interacted physically with Ptgs2 mRNA. Igf2bp1 expression was induced exclusively in wound-bed cMSCs, and full induction of Ptgs2 and Igf2bp1 during repair required Myd88.

Conclusions

We identified Igf2bp1 as a regulator of Ptgs2 mRNA in mice. Igf2bp1 is required for full induction of Ptgs2 mRNA in cMSCs."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.org/dc/terms/identifier"doi:10.1053/j.gastro.2012.03.037"xsd:string
http://purl.uniprot.org/citations/22465430http://purl.org/dc/terms/identifier"doi:10.1053/j.gastro.2012.03.037"xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Miyoshi H."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Miyoshi H."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Stappenbeck T.S."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Stappenbeck T.S."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Drylewicz M.R."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Drylewicz M.R."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Manieri N.A."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/author"Manieri N.A."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/name"Gastroenterology"xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/name"Gastroenterology"xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/pages"110-121"xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/pages"110-121"xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/title"Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem cells in mice."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/title"Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem cells in mice."xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/volume"143"xsd:string
http://purl.uniprot.org/citations/22465430http://purl.uniprot.org/core/volume"143"xsd:string
http://purl.uniprot.org/citations/22465430http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22465430
http://purl.uniprot.org/citations/22465430http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22465430
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