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Changes in the expression of genes related to apoptosis and fibrosis pathways in CCl4-treated rats

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Abstract

Chronic liver diseases are accompanied by changes in the biochemical pathways related to the regulation of apoptosis and extra-cellular matrix deposition. The present study was designed to investigate, using low density arrays, changes in the hepatic gene expression together with hepatic biochemical and histological alterations in rats that had liver impairment induced by chronic exposure to CCl4. Further, we examined the possible recovery of genetic and pathological changes following the cessation of the hepatotoxic injury. Experimental fibrosis was induced in male Wistar rats by CCl4 administration. Animals were subdivided into two groups. One group was given CCl4 and animals were killed at 8 and 12 weeks of treatment. The other group was treated with CCl4 for 6 weeks, the CCl4 was then stopped and, subsequently, subgroups of animals were killed after 1 and 2 weeks of recovery. CCl4 administration over 12 weeks was associated with significant changes in B-cell leukemia/lymphoma 2, procollagen type I α 2, matrix metalloproteinases 3 and 8, tissue inhibitors of metalloproteinases 1, 2, and 3 and the inhibitor of apoptosis 4 gene expressions. Recovery after CCl4 cessation was associated with changes in procollagen type I α 2, matrix metalloproteinase 7, tissue inhibitors of metalloproteinases 1 and 2, inhibitor of apoptosis 4, and survivin gene expressions. This study shows an association between changes in the expression of several genes regulating hepatic cell apoptosis, the fibrosis process, and the recovery of the hepatic function after removal of the toxic injury.

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Acknowledgments

Supported by grants from Fondo de Investigación Sanitaria (FIS 00/0232, 02/0430, 05/1607) and Redes de Centros from the Instituto de Salud Carlos III (C03/08 and RD06). Natàlia Ferré is a post-doctoral researcher fellow funded by the Juan de la Cierva program of the Ministerio de Educación y Ciencia, Madrid, Spain. Judit Marsillach is the recipient of a post-graduate research fellowship from the Generalitat de Catalunya (FI 05/00068). The authors are indebted to Mònica Monterde and Esther Tous for their invaluable technical support. Editorial assistance was provided by Dr Peter R. Turner of t-SciMed, Reus, Spain.

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Authors and Affiliations

  1. Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut de Recerca en Ciències de la Salut, C. Sant Joan s/n, 43201, Reus (Catalunya), Spain

    Judit Marsillach, Jordi Camps, Anna Rull, Raul Beltran & Jorge Joven

  2. Department of Clinical Biochemistry and Molecular Genetics, Hospital Clínic Universitari, C. Villarroel 170, 08036, Barcelona, Spain

    Natàlia Ferré

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  1. Judit Marsillach
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  2. Natàlia Ferré
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Correspondence to Jordi Camps.

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Marsillach, J., Ferré, N., Camps, J. et al. Changes in the expression of genes related to apoptosis and fibrosis pathways in CCl4-treated rats. Mol Cell Biochem 308, 101–109 (2008). https://doi.org/10.1007/s11010-007-9617-0

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  • DOI: https://doi.org/10.1007/s11010-007-9617-0

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