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ErbB Signaling Is R...
ErbB Signaling Is Required for the Proliferative Actions of GLP-2 in the Murine Gut
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- Yusta, Bernardo (author)
- Mount Sinai Hospital of University of Toronto
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- Holland, Dianne (author)
- Mount Sinai Hospital of University of Toronto
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- Koehler, Jacqueline A. (author)
- Mount Sinai Hospital of University of Toronto
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- Maziarz, Marlena (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine,Mount Sinai Hospital of University of Toronto
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- Estall, Jennifer L. (author)
- Mount Sinai Hospital of University of Toronto
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- Higgins, Rachel (author)
- Mount Sinai Hospital of University of Toronto
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- Drucker, Daniel J. (author)
- Mount Sinai Hospital of University of Toronto
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(creator_code:org_t)
- Elsevier BV, 2009
- 2009
- English 11 s.
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In: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 137:3, s. 986-996
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- Background & Aims: Glucagon-like peptide-2 (GLP-2) is a 33-amino acid peptide hormone secreted by enteroendocrine cells in response to nutrient ingestion. GLP-2 stimulates crypt cell proliferation leading to expansion of the mucosal epithelium; however, the mechanisms transducing the trophic effects of GLP-2 are incompletely understood. Methods: We examined the gene expression profiles and growth-promoting actions of GLP-2 in normal mice in the presence or absence of an inhibitor of ErbB receptor signaling, in Glp2r-/- mice and in Egfrwa2 mice harboring a hypomorphic point mutation in the epidermal growth factor receptor. Results: Exogenous GLP-2 administration rapidly induced the expression of a subset of ErbB ligands including amphiregulin, epiregulin, and heparin binding (HB)-epidermal growth factor, in association with induction of immediate early gene expression in the small and large bowel. These actions of GLP-2 required a functional GLP-2 receptor because they were eliminated in Glp2r-/- mice. In contrast, insulin-like growth factor-I and keratinocyte growth factor, previously identified mediators of GLP-2 action, had no effect on the expression of these ErbB ligands. The GLP-2-mediated induction of ErbB ligand expression was not metalloproteinase inhibitor sensitive but was significantly diminished in Egfrwa2 mice and completed abrogated in wild-type mice treated with the pan-ErbB inhibitor CI-1033. Furthermore, the stimulatory actions of GLP-2 on crypt cell proliferation and bowel growth were eliminated in the presence of CI-1033. Conclusions: These findings identify the ErbB signaling network as a target for GLP-2 action leading to stimulation of growth factor-dependent signal transduction and bowel growth in vivo.
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