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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
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1437-4315
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Volume 394, Issue 9

Issues

Changes in COX-2 and oxidative damage factors during differentiation of human mesenchymal stem cells to hepatocyte-like cells is associated with downregulation of P53 gene

Safoura Khajeniazi
  • Faculty of Medical Sciences, Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Abdolamir Allameh
  • Corresponding author
  • Faculty of Medical Sciences, Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Masoud Soleimani
  • Faculty of Medical Sciences, Department of Hematology, Tarbiat Modares University, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Esmaeil Mortaz
  • National Research Institute of Tuberculosis and Lung Disease (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Division of Pharmacology and Pathophysiology Utrecht Institute for Pharmaceutical Sciences Faculty of Sciences, Utrecht University, NL-3508 TB Utrecht, the Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-04-11 | DOI: https://doi.org/10.1515/hsz-2012-0355

Abstract

Differentiation of human mesenchymal stem cells (MSCs) to metabolically active hepatocytes depends on different regulatory factors. Trans-differentiation of stem cells into specific cell lineage in the presence of specific stimuli is associated with the molecular and cellular damage. The aim of the present study was to examine the role of P53 in the regulation of cyclooxygenase-2 (COX-2) expression and the generation of protein and lipid oxidation during trans-differentiation of MSCs into hepatocyte-like cells. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers was associated with increased levels of lipid peroxidation and protein carbonyl formation. Expression of P53 and COX-2 at mRNA and protein levels were evaluated in MSCs before and after differentiation on days 7, 14 and 21. We showed that the up-regulation of COX-2 was associated with augmentation of the rate of cell proliferation, morphological and biochemical changes of hepatocytes-like cells. However, in parallel the P53 at the mRNA level was down-regulated, and at protein levels accumulation in the nuclei was reduced during the hepatogenic differentiation time. Our results may suggest a P53-COX-2 pathway in the regulation of hepatogenic differentiation of stem cells, which is linked to differentiation-dependent molecular oxidative damage.

Keywords: COX-2; differentiation; hepatocytes; oxidative damage; P53; stem cells

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About the article

Corresponding author: Abdolamir Allameh, Faculty of Medical Sciences, Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran


Received: 2012-12-20

Accepted: 2013-04-02

Published Online: 2013-04-11

Published in Print: 2013-09-01


Citation Information: Biological Chemistry, Volume 394, Issue 9, Pages 1213–1222, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2012-0355.

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