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Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration
The well‐known action of the gastric hormone gastrin in stimulating gastric acid secretion is mediated by activation of cholecystokinin‐2 receptors (CCK2R). The latter are expressed by a variety of cell types suggesting that gastrin is implicated in multiple functions. During wound healing in the st...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641928/ https://www.ncbi.nlm.nih.gov/pubmed/29038353 http://dx.doi.org/10.14814/phy2.13394 |
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author | Varga, Akos Kumar, Jothi Dinesh Simpson, Alec W.M. Dodd, Steven Hegyi, Peter Dockray, Graham J. Varro, Andrea |
author_facet | Varga, Akos Kumar, Jothi Dinesh Simpson, Alec W.M. Dodd, Steven Hegyi, Peter Dockray, Graham J. Varro, Andrea |
author_sort | Varga, Akos |
collection | PubMed |
description | The well‐known action of the gastric hormone gastrin in stimulating gastric acid secretion is mediated by activation of cholecystokinin‐2 receptors (CCK2R). The latter are expressed by a variety of cell types suggesting that gastrin is implicated in multiple functions. During wound healing in the stomach CCK2R may be expressed by myofibroblasts. We have now characterized CCK2R expression in cultured myofibroblasts. Immunocytochemistry showed that a relatively small proportion (1–6%) of myofibroblasts expressed the receptor regardless of the region of the gut from which they were derived, or whether from cancer or control tissue. Activation of CCK2R by human heptadecapeptide gastrin (hG17) increased intracellular calcium concentrations in a small subset of myofibroblasts indicating the presence of a functional receptor. Unexpectedly, we found over 80% of cells expressing CCK2R were also labeled with 5‐ethynyl‐2′‐deoxyuridine (EdU) which is incorporated into DNA during S‐phase of the cell cycle. hG17 did not stimulate EdU incorporation but increased migration of both EdU‐labeled and unlabelled myofibroblasts; the migratory response was inhibited by a CCK2R antagonist and by an inhibitor of IGF receptor tyrosine kinase; hG17 also increased IGF‐2 transcript abundance. The data suggest myofibroblasts express CCK2R in a restricted period of the cell cycle during S‐phase, and that gastrin accelerates migration of these cells; it also stimulates migration of adjacent cells probably through paracrine release of IGF. Together with previous findings, the results raise the prospect that gastrin controls the position of dividing myofibroblasts which may be relevant in wound healing and cancer progression in the gastrointestinal tract. |
format | Online Article Text |
id | pubmed-5641928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56419282017-10-18 Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration Varga, Akos Kumar, Jothi Dinesh Simpson, Alec W.M. Dodd, Steven Hegyi, Peter Dockray, Graham J. Varro, Andrea Physiol Rep Original Research The well‐known action of the gastric hormone gastrin in stimulating gastric acid secretion is mediated by activation of cholecystokinin‐2 receptors (CCK2R). The latter are expressed by a variety of cell types suggesting that gastrin is implicated in multiple functions. During wound healing in the stomach CCK2R may be expressed by myofibroblasts. We have now characterized CCK2R expression in cultured myofibroblasts. Immunocytochemistry showed that a relatively small proportion (1–6%) of myofibroblasts expressed the receptor regardless of the region of the gut from which they were derived, or whether from cancer or control tissue. Activation of CCK2R by human heptadecapeptide gastrin (hG17) increased intracellular calcium concentrations in a small subset of myofibroblasts indicating the presence of a functional receptor. Unexpectedly, we found over 80% of cells expressing CCK2R were also labeled with 5‐ethynyl‐2′‐deoxyuridine (EdU) which is incorporated into DNA during S‐phase of the cell cycle. hG17 did not stimulate EdU incorporation but increased migration of both EdU‐labeled and unlabelled myofibroblasts; the migratory response was inhibited by a CCK2R antagonist and by an inhibitor of IGF receptor tyrosine kinase; hG17 also increased IGF‐2 transcript abundance. The data suggest myofibroblasts express CCK2R in a restricted period of the cell cycle during S‐phase, and that gastrin accelerates migration of these cells; it also stimulates migration of adjacent cells probably through paracrine release of IGF. Together with previous findings, the results raise the prospect that gastrin controls the position of dividing myofibroblasts which may be relevant in wound healing and cancer progression in the gastrointestinal tract. John Wiley and Sons Inc. 2017-10-16 /pmc/articles/PMC5641928/ /pubmed/29038353 http://dx.doi.org/10.14814/phy2.13394 Text en © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Varga, Akos Kumar, Jothi Dinesh Simpson, Alec W.M. Dodd, Steven Hegyi, Peter Dockray, Graham J. Varro, Andrea Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration |
title | Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration |
title_full | Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration |
title_fullStr | Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration |
title_full_unstemmed | Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration |
title_short | Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration |
title_sort | cell cycle dependent expression of the cck2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641928/ https://www.ncbi.nlm.nih.gov/pubmed/29038353 http://dx.doi.org/10.14814/phy2.13394 |
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