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Longitudinal Analysis of Gene Expression in Porcine Skeletal Muscle After Post-Injection Local Injury
Authors: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
Affiliation:(1) UMR181 de Physiopathologie et Toxicologie Expérimentales, INRA, ENVT, National Veterinary School, 23 chemin des Capelles, BP 87614, Toulouse cedex 03, 31076, France;(2) UR 444 Cellular Genetics. INRA, Castanet-Tolosan, France;(3) U466 Cell Regulation: Lipidoses and Atherosclerosis, Department of Pathology, INSERM, CHU Rangueil, Toulouse, France
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. PJF and LL contributed equally to this work and both should be considered as first authors.
Keywords:gene expression profiling  injury  intramuscular injection  local tolerance  pathophysiology
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