Abstract
Reactive cholangiocytes acquire a neuroendocrine-like phenotype, with synthesis and local release of neuropeptides and hormones. The mechanism that drives such phenotypical changes is still undefined. Pancreatic Duodenal Homeobox-1 (PDX-1) is a transcription factor required for pancreatic development, that sustains pancreatic beta-cell response to injury and insulin synthesis. PDX-1 induces neuroendocrine-like transition of pancreatic ductal cells. Cholangiocyte response to injury is modulated by Glucagon-Like Peptide-1 Receptor (GLP-1R), which, in the pancreas, activates PDX-1. We wanted to verify whether PDX-1 plays any role in cholangiocyte neuroendocrine-like transdifferentiation in response to injury. PDX-1 expression was assessed in cholangiocytes from normal and one week bile duct ligated (BDL) rats. Changes in PDX-1 expression and activation upon GLP-1R activation were then assayed. The effects of the lack of PDX-1 in cholangiocytes were studied in vitro by siRNA and in vivo by the employment of PDX-1-deficient (+/-) mice. BDL but not normal cholangiocytes express PDX-1. GLP-1R activation elicits, in a PI3K-dependent fashion, PDX-1 expression, together with its nuclear translocation. In vitro, GLP-1R-induced increases i...Continue Reading
References
Apr 29, 1998·Nature·S DuttaC Wright
Dec 16, 1998·Microscopy Research and Technique·L Rosenberg
May 10, 2000·Nature Medicine·S FerberA Karasik
Dec 31, 2002·Journal of Pediatric Endocrinology & Metabolism : JPEM·Danielle MelloulDavid Zangen
Oct 11, 2003·Biochemical and Biophysical Research Communications·T MiyatsukaM Hori
Nov 3, 2004·Gastroenterology·Konstantinos N LazaridisNicholas F Larusso
Dec 25, 2004·The International Journal of Biochemistry & Cell Biology·Anne Grapin-Botton
May 12, 2005·Molecular and Cellular Endocrinology·Violeta StanojevicMelissa K Thomas
May 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Tamar SapirSarah Ferber
Jul 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kumar ShanmukhappaJorge A Bezerra
Aug 9, 2005·Journal of Hepatology·Domenico AlvaroEugenio Gaudio
Sep 13, 2005·Surgery·Masayuki KoizumiMasayuki Imamura
Mar 15, 2006·Gastroenterology·Akihisa FukudaTsutomu Chiba
Mar 22, 2006·Best Practice & Research. Clinical Gastroenterology·Anirban MaitraRalph H Hruban
Apr 1, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Eugenio GaudioGianfranco Alpini
Apr 19, 2006·Gastroenterology·Eugenio GaudioGianfranco Alpini
Oct 24, 2006·The Journal of Biological Chemistry·Therese B DeramaudtAnil K Rustgi
Jan 24, 2007·Gastroenterology·Domenico AlvaroGianfranco Alpini
May 9, 2007·Gastroenterology·Samuele De MinicisRobert F Schwabe
May 15, 2007·Gastroenterology·Laurie L Baggio, Daniel J Drucker
Jul 17, 2007·Gastroenterology·Marco MarzioniAntonio Benedetti
Aug 21, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Irit Meivar-LevySarah Ferber
Oct 3, 2007·Annals of Internal Medicine·Domenico AlvaroAntonio Benedetti
Oct 3, 2008·Gut·M MarzioniA Benedetti
Dec 26, 2008·BMC Research Notes·Juliette Cuvelier DelisleVanessa Louzier
Jun 13, 2009·Gut·Ulrich Beuers, Burkhard Göke
Citations
Feb 3, 2011·World Journal of Surgery·Courtney J BalentineF Charles Brunicardi
Aug 15, 2015·Cellular and Molecular Gastroenterology and Hepatology·Luca MaroniGianfranco Alpini
Sep 4, 2012·Liver International : Official Journal of the International Association for the Study of the Liver·Samuele De MinicisGianluca Svegliati-Baroni
Jun 14, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marco MarzioniGianluca Svegliati Baroni
Dec 5, 2012·Journal of Hepatology·Marco MarzioniAntonio Benedetti
Jul 16, 2013·The American Journal of Pathology·Samuele De MinicisGianluca Svegliati-Baroni
Jun 27, 2017·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Keisaku SatoGianfranco Alpini
Oct 3, 2018·International Journal of Molecular Sciences·Debora Maria GiordanoMarco Marzioni
Dec 19, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Luca MaroniMarco Marzioni
Jul 17, 2013·Experimental Biology and Medicine·Yuyan HanAntonio Franchitto
Sep 4, 2015·Pancreas·Jennifer-Ann BayanBangyan L Stiles
Jul 29, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Matthew McMillinGianfranco Alpini