Pancreatic Duodenal Homeobox-1 de novo expression drives cholangiocyte neuroendocrine-like transdifferentiation

Journal of Hepatology
Marco MarzioniAntonio Benedetti

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

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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
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

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