Martín-Sanz P, Mayoral R, Casado M, Boscá L. COX-2 in liver, from regeneration to hepatocarcinogenesis: What we have learned from animal models? World J Gastroenterol 2010; 16(12): 1430-1435 [PMID: 20333781 DOI: 10.3748/wjg.v16.i12.1430]
Corresponding Author of This Article
Dr. Lisardo Boscá, Department of Metabolism and Cell Signaling, Institute of Biomedical Research “Alberto Sols” (CSIC-UAM), Arturo Duperier 4, Madrid 28029, Spain. lbosca@iib.uam.es
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World J Gastroenterol. Mar 28, 2010; 16(12): 1430-1435 Published online Mar 28, 2010. doi: 10.3748/wjg.v16.i12.1430
COX-2 in liver, from regeneration to hepatocarcinogenesis: What we have learned from animal models?
Paloma Martín-Sanz, Rafael Mayoral, Marta Casado, Lisardo Boscá
Paloma Martín-Sanz, Rafael Mayoral, Marta Casado, Lisardo Boscá, Biomedical Network Center for the Study of Hepatic and Digestive Diseases (CIBERehd), Villarroel 170, Barcelona 08036, Spain
Paloma Martín-Sanz, Rafael Mayoral, Lisardo Boscá, Department of Metabolism and Cell Signaling, Institute of Biomedical Research “Alberto Sols” (CSIC-UAM), Arturo Duperier 4, Madrid 28029, Spain
Marta Casado, Department of Pathology and Molecular and Cellular Therapy, Institute of Biomedicine of Valencia (IBV-CSIC), Jaume Roig 11, Valencia 46010, Spain
Author contributions: Martín-Sanz P and Boscá L contributed equally to writing of the paper; Mayoral R and Casado M performed the experiments in support of the work. All authors analyzed the data and discussed the biological relevance of the animal models.
Supported by Grant BFU2008-02161 and SAF2007-60551 from MICINN, S-BIO-0283/2006 from Comunidad de Madrid and FIS-RECAVA RD06/0014/0025. RECAVA and CIBERehd are funded by the Instituto de Salud Carlos III
Correspondence to: Dr. Lisardo Boscá, Department of Metabolism and Cell Signaling, Institute of Biomedical Research “Alberto Sols” (CSIC-UAM), Arturo Duperier 4, Madrid 28029, Spain. lbosca@iib.uam.es
Telephone: +34-91-4972747 Fax: +34-91-5854401
Received: December 17, 2009 Revised: January 15, 2010 Accepted: January 22, 2010 Published online: March 28, 2010
Abstract
The use of animals lacking genes or expressing genes under the control of cell-specific promoters has significantly increased our knowledge of the genetic and molecular basis of physiopathology, allowing testing of functional hypotheses and validation of biochemical and pharmacologic approaches in order to understand cell function. However, with unexpected frequency, gene knockout animals and, more commonly, animal models of transgenesis give experimental support to even opposite conclusions on gene function. Here we summarize what we learned on the role of cyclooxygenase 2 (COX-2) in liver and revise the results obtained in 3 independent models of mice expressing a COX-2 transgene specifically in the hepatocyte. Upon challenge with pro-inflammatory stimuli, the animals behave very differently, some transgenic models having a protective effect but others enhancing the injury. In addition, one transgene exerts differential effects on normal liver physiology depending on the transgenic animal model used.
