{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:09:23Z","timestamp":1761844163490,"version":"3.44.0"},"reference-count":23,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2012,2,22]]},"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>In the intestine Hedgehog (Hh) signalling is directed from epithelium to mesenchyme and negatively regulates epithelial precursor cell fate. The role of Hh signalling in the oesophagus has not been studied in vivo. Here the authors examined the role of Hh signalling in epithelial homeostasis of oesophagus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>The authors used transgenic mice in which the Hh receptor <jats:italic>Patched1<\/jats:italic> (<jats:italic>Ptch1<\/jats:italic>) could be conditionally inactivated in a body-wide manner and mice in which <jats:italic>Gli1<\/jats:italic> could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in patients with oesophageal squamous cell carcinoma (SCC) by quantitative real-time PCR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Sonic Hh is signalled in an autocrine manner in the basal layer of the oesophagus. Activation of Hh signalling resulted in an expansion of the epithelial precursor cell compartment and failure of epithelial maturation and migration. Levels of Hh targets <jats:italic>GLI1, HHIP<\/jats:italic> and <jats:italic>PTCH1<\/jats:italic> were increased in SCC compared with normal tissue from the same patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Here the authors find that Hh signalling positively regulates the precursor cell compartment in the oesophageal epithelium in an autocrine manner. Since Hh signalling targets precursor cells in the oesophageal epithelium and signalling is increased in SCCs, Hh signalling may be involved in oesophageal SCC formation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gutjnl-2011-301141","type":"journal-article","created":{"date-parts":[[2012,4,13]],"date-time":"2012-04-13T20:51:39Z","timestamp":1334350299000},"page":"348-357","source":"Crossref","is-referenced-by-count":19,"title":["Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus"],"prefix":"10.1136","volume":"62","author":[{"given":"Willemijn A","family":"van Dop","sequence":"first","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands"},{"name":"Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanne L","family":"Rosekrans","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands"},{"name":"Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Uhmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viljar","family":"Jaks","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G Johan A","family":"Offerhaus","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands"},{"name":"Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius A","family":"van den Bergh Weerman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Kasper","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarom","family":"Heijmans","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands"},{"name":"Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C H","family":"Hardwick","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hein W","family":"Verspaget","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan W","family":"Hommes","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Center for Inflammatory Bowel Diseases, University of California Los Angeles, Los Angeles, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rune","family":"Toftg\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Hahn","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gijs R","family":"van den Brink","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands"},{"name":"Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2012,4,13]]},"reference":[{"key":"2025090714303355000_62.3.348.1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00054.2006"},{"key":"2025090714303355000_62.3.348.2","doi-asserted-by":"publisher","DOI":"10.1038\/1717"},{"key":"2025090714303355000_62.3.348.3","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1242\/dev.127.12.2763","article-title":"Hedgehog signals regulate multiple aspects of gastrointestinal development","volume":"127","author":"Ramalho-Santos","year":"2000","journal-title":"Development"},{"key":"2025090714303355000_62.3.348.4","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1994.1097"},{"key":"2025090714303355000_62.3.348.5","doi-asserted-by":"publisher","DOI":"10.1038\/1711"},{"key":"2025090714303355000_62.3.348.6","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24400"},{"key":"2025090714303355000_62.3.348.7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.05.002"},{"key":"2025090714303355000_62.3.348.8","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.02.068"},{"key":"2025090714303355000_62.3.348.9","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.01.048"},{"key":"2025090714303355000_62.3.348.10","doi-asserted-by":"publisher","DOI":"10.1159\/000098111"},{"key":"2025090714303355000_62.3.348.11","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-010-9337-8"},{"key":"2025090714303355000_62.3.348.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905360"},{"key":"2025090714303355000_62.3.348.13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-075648"},{"key":"2025090714303355000_62.3.348.14","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00019.2007"},{"key":"2025090714303355000_62.3.348.15","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00144.x"},{"key":"2025090714303355000_62.3.348.16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704280200"},{"key":"2025090714303355000_62.3.348.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.023"},{"key":"2025090714303355000_62.3.348.18","doi-asserted-by":"publisher","DOI":"10.1038\/5007"},{"key":"2025090714303355000_62.3.348.19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022620"},{"key":"2025090714303355000_62.3.348.20","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.5.628"},{"key":"2025090714303355000_62.3.348.21","doi-asserted-by":"publisher","DOI":"10.1038\/nm0797-788"},{"key":"2025090714303355000_62.3.348.22","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1619"},{"key":"2025090714303355000_62.3.348.23","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.23.090506.123357"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gutjnl-2011-301141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T21:30:38Z","timestamp":1757280638000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gutjnl-2011-301141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,13]]},"references-count":23,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2013,1,31]]},"published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1136\/gutjnl-2011-301141"],"URL":"https:\/\/doi.org\/10.1136\/gutjnl-2011-301141","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[2012,4,13]]}}}