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Licensed Unlicensed Requires Authentication Published by De Gruyter November 17, 2009

Dexamethasone-dependent versus -independent markers of epithelial to mesenchymal transition in primary hepatocytes

  • Patricio Godoy , Sumathi Lakkapamu , Markus Schug , Alexander Bauer , Joanna D. Stewart , Essam Bedawi , Seddik Hammad , Jakia Amin , Rosemarie Marchan , Wiebke Schormann , Lindsey Maccoux , Iris von Recklinghausen , Raymond Reif and Jan G. Hengstler
From the journal Biological Chemistry

Abstract

Recently, epithelial to mesenchymal transition (EMT) has been shown to represent a feature of dedifferentiating hepatocytes in vitro. Three-dimensional soft collagen gels can antagonize but not completely abolish this effect. Hormonal additives to culture media are known to maintain differentiated hepatocyte functions. Therefore, we studied whether insulin and dexamethasone antagonize EMT in cultured hepatocytes. Both hormones antagonized but not completely abolished certain morphological features of EMT. Dexamethasone antagonized acquisition of fibroblastoid shape, whereas insulin favored bile canaliculi formation. In a subsequent step, we analyzed expression of a battery of EMT-related genes. Of all markers tested, vimentin and snail-1 correlated best with morphological features of EMT. Interestingly, dexamethasone reduced expression levels of both vimentin and snail-1, whereas the influence of insulin was less pronounced. An important result of this study is that 12 out of 17 analyzed EMT markers were transcriptionally influenced by dexamethasone (vimentin, snail-1, snail-2, HNF4α, Twist-1, ZEB2, fibronectin, occludin, MMP14, claudin-1, cytokeratin-8, and cytokeratin-18), whereas the remaining factors seemed to be less dependent on dexamethasone. In conclusion, EMT markers in hepatocytes can be classified as dexamethasone-dependent versus -independent.


Corresponding author

Received: 2009-4-15
Accepted: 2009-9-24
Published Online: 2009-11-17
Published in Print: 2010-01-01

©2010 by Walter de Gruyter Berlin New York

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