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

被引：41

作者：

Godoy, Patricio ^{[1
]}

Lakkapamu, Sumathi ^{[1
]}

Schug, Markus ^{[1
]}

Bauer, Alexander ^{[1
]}

Stewart, Joanna D. ^{[1
]}

Bedawi, Essam ^{[1
]}

Hammad, Seddik ^{[1
]}

Amin, Jakia ^{[1
]}

Marchan, Rosemarie ^{[1
]}

Schormann, Wiebke ^{[1
]}

Maccoux, Lindsey ^{[1
]}

von Recklinghausen, Iris ^{[1
]}

Reif, Raymond ^{[1
]}

Hengstler, Jan G. ^{[1
]}

机构：

[1] Leibniz Res Ctr Working Environm & Human Factors, D-44139 Dortmund, Germany

来源：

BIOLOGICAL CHEMISTRY | 2010年 / 391卷 / 01期

关键词：

dexamethasone; epithelial to mesenchymal transition; extracellular matrix; gene expression; hepatocytes; insulin; PRIMARY RAT HEPATOCYTES; IN-VITRO SYSTEM; ENZYME-INDUCTION; SIGNAL-TRANSDUCTION; TUMOR-METASTASIS; GENE-EXPRESSION; UP-REGULATION; MOUSE LIVERS; STEM-CELLS; TGF-BETA;

D O I：

10.1515/BC.2010.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 ill hepatocytes call be classified as dexamethasone-dependent versus -independent.

引用

页码：73 / 83

页数：11

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