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

Dexamethasone-dependent versus -independent markers of epithelial to mesenchymal transition in primary hepatocytes
Dexamethasone-dependent versus -independent markers of epithelial to mesenchymal transition in primary hepatocytes
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, HNF4 alpha, 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.
1431-6730
73-83
Godoy, Patricio
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Lakkapamu, Sumathi
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Schug, Markus
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Bauer, Alexander
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Stewart, Joanna D.
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Bedawi, Essam
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Hammad, Seddik
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Amin, Jakia
529ba300-3a07-4ed1-9f32-a310ba7bfdae
Marchan, Rosemarie
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Schormann, Wiebke
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Maccoux, Lindsey
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von Recklinghausen, Iris
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Reif, Raymond
624c3f37-6aab-4339-bf3e-cd9ace305e7a
Hengstler, Jan G.
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Godoy, Patricio
b3dce4c3-6eca-45ab-bfeb-c4800cfdeb97
Lakkapamu, Sumathi
8580c69d-5fdc-4ff5-acf5-3be6960b0023
Schug, Markus
7f4a803c-f33a-46be-855c-c5d06ffa1b43
Bauer, Alexander
5c0b7c40-ba76-401f-b0ff-b4ff843778dd
Stewart, Joanna D.
e1ec9784-39cc-48ed-9f4f-2a05d25f2106
Bedawi, Essam
4b0e643d-7700-46bc-bc13-7e9acb63addd
Hammad, Seddik
80222dc0-17ab-4e82-a7e6-30fba9f95691
Amin, Jakia
529ba300-3a07-4ed1-9f32-a310ba7bfdae
Marchan, Rosemarie
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Schormann, Wiebke
b14d2d98-98c8-4ed3-885f-bc30d8b4d167
Maccoux, Lindsey
cbb83c40-5dce-4527-b0df-8f2eb1b39c26
von Recklinghausen, Iris
a41a4423-2b6a-4fab-94cd-c3f31d5c39a1
Reif, Raymond
624c3f37-6aab-4339-bf3e-cd9ace305e7a
Hengstler, Jan G.
8b1695f3-3506-400f-85ae-44b875949445

Godoy, Patricio, Lakkapamu, Sumathi, Schug, Markus, Bauer, Alexander, Stewart, Joanna D., Bedawi, Essam, Hammad, Seddik, Amin, Jakia, Marchan, Rosemarie, Schormann, Wiebke, Maccoux, Lindsey, von Recklinghausen, Iris, Reif, Raymond and Hengstler, Jan G. (2010) Dexamethasone-dependent versus -independent markers of epithelial to mesenchymal transition in primary hepatocytes. Biological Chemistry, 391 (1), 73-83. (doi:10.1515/bc.2010.010). (PMID:20064087)

Record type: Article

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, HNF4 alpha, 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.

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Published date: January 2010
Organisations: Centre for Biological Sciences

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Local EPrints ID: 355917
URI: http://eprints.soton.ac.uk/id/eprint/355917
ISSN: 1431-6730
PURE UUID: 87a0f993-db85-480d-a662-c5ce9c4930fe
ORCID for Joanna D. Stewart: ORCID iD orcid.org/0000-0002-2608-1967

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Date deposited: 04 Sep 2013 17:02
Last modified: 18 Feb 2021 17:20

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Contributors

Author: Patricio Godoy
Author: Sumathi Lakkapamu
Author: Markus Schug
Author: Alexander Bauer
Author: Joanna D. Stewart ORCID iD
Author: Essam Bedawi
Author: Seddik Hammad
Author: Jakia Amin
Author: Rosemarie Marchan
Author: Wiebke Schormann
Author: Lindsey Maccoux
Author: Iris von Recklinghausen
Author: Raymond Reif
Author: Jan G. Hengstler

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