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Pharmaceutical Research

, Volume 24, Issue 8, pp 1480–1489 | Cite as

Longitudinal Analysis of Gene Expression in Porcine Skeletal Muscle After Post-Injection Local Injury

  • Pierre J. Ferré
  • Laurence Liaubet
  • Didier Concordet
  • Magali SanCristobal
  • Emmanuelle Uro-Coste
  • Gwenola Tosser-Klopp
  • Agnès Bonnet
  • Pierre-Louis Toutain
  • François Hatey
  • Hervé P. Lefebvre
Research Paper

Abstract

Purpose

The purpose of this study is to describe the time course of gene expression in a skeletal muscle local injury induced by an intramuscular (IM) injection, and to compare the dynamics of gene expression with pathological events.

Materials and Methods

Ten piglets received 4 IM injections of propylene glycol in the longissimus dorsi muscles 6 h, 2, 7, and 21 days before euthanasia, where control and injected muscle sites were sampled for RNA isolation and microscopic examination. The hybridization of nylon cDNA microarrays was carried out with radioactive probes obtained from the muscle RNA.

Results

153 genes were found under- or over-expressed at least once among the investigated time-conditions. The eight most discriminant genes were also identified: Two genes (GTP-binding protein RAD and Ankyrin repeat domain protein) were over-expressed at 6 h and six genes between 2 and 21 days (Osteonectin, Fibronectin, Matrix metalloproteinase-2, Collagen alpha 1(I) chain, Collagen alpha 2(I) chain, and Thymosin beta-4). Necrosis, inflammation and regeneration were observed through both the dynamics of gene expression profiles and through the microscopic examinations.

Conclusion

Our data demonstrate that several pathways are involved in post-injection muscle injury, and that necrosis, inflammation and regeneration are not sequential but occur in parallel.

Key words

gene expression profiling injury intramuscular injection local tolerance pathophysiology 

Notes

Acknowledgements

The muscle specific cDNA library used in this work was kindly provided by Christian Bendixen. The authors thank Rémi Houlgatte (TAGC, Marseille, France) for critical discussions about/on Nylon microarray methodology and data analysis. We thank Jean-Pierre Gau, Nadine Gautier, Francis Benne, and Janine Rallières for their technical assistance. We wish to acknowledge support from the CRGS platform of the Toulouse Midi-Pyrenees Genopole (Cécile Donnadieu-Tonon) (http://genopole-toulouse.prd.fr/), where the nylon membranes were produced. The database with BASE software for MIAME submission was developed by Christelle Dantec and managed by a computer group (SIGENAE, Système d’information du projet d’analyse des génomes des animaux d’élevage, http://www.sigenae.org). We thank the work group for statistical analysis of microarray data (Philippe Besse, Alain Baccini, Sébastien Déjean, http://www.lsp.ups-tlse.fr/Programmes/Biopuces/) for their advice in the RF analysis and to Christèle Robert-Granié for helpful discussions on the statistical methods.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Pierre J. Ferré
    • 1
  • Laurence Liaubet
    • 2
  • Didier Concordet
    • 1
  • Magali SanCristobal
    • 2
  • Emmanuelle Uro-Coste
    • 3
  • Gwenola Tosser-Klopp
    • 2
  • Agnès Bonnet
    • 2
  • Pierre-Louis Toutain
    • 1
  • François Hatey
    • 2
  • Hervé P. Lefebvre
    • 1
  1. 1.UMR181 de Physiopathologie et Toxicologie Expérimentales, INRA, ENVTNational Veterinary SchoolToulouse cedex 03France
  2. 2.UR 444 Cellular Genetics. INRACastanet-TolosanFrance
  3. 3.U466 Cell Regulation: Lipidoses and Atherosclerosis, Department of PathologyINSERMCHU Rangueil, ToulouseFrance

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