Inflammatory Mediators and Skeletal Muscle Injury: A DNA Microarray Analysis

Abstract

Traumatic skeletal muscle injury causes a specific sequence of cellular events consisting of degeneration, inflammation, regeneration, and fibrosis. The role of early posttraumatic mechanisms, including acute inflammatory response, in muscle repair is not well understood. In the present study, oligonucleotide microarray analyses were used to examine the candidate genes that are involved in these early events of the muscle injury/repair process. cDNA was prepared from the injured and control tibialis anterior (TA) muscle of mice 24 h postinjury and labeled with the fluorescent dye Cy5 or Cy3 prior to hybridization to a DNA microarray. The microarray analysis, including 732 genes, was conducted in triplicate, and we describe only genes modulated by the injury showing a differential expression (both increased and decreased) 1.7-fold or greater (p < 0.05) from control uninjured TA muscle. Selected expression patterns were confirmed by other gene expression detection methods, including real-time reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA) or immunohistochemistry detection methods. The upregulated genes (2.8%) were mainly associated with inflammation, oxidative stress, and cell proliferation, whereas the downregulated genes (3.2%) were related to metabolic and cell signaling pathways. In addition, the study suggested that chemokines, such as monocyte chemoattractant protein-1 (MCP-1), associated with monocyte/macrophage influx and activation, are abundantly expressed in postinjured muscle, and they might play a role in traumatic muscle injury/recovery processes.

Global analysis of gene expression inXenopushindlimbs during stage‐dependent complete and incomplete regeneration

“…The results of eight previously published regeneration-related genomic analyses were selected for comparison to the microarray results (Ishino et al, 2003;King et al, 2003;Summan et al, 2003;Katogi et al, 2004;Swamy et al, 2004;Wolfe et al, 2004;Reddien et al, 2005;Schnapp et al, 2005;Tazaki et al, 2005). Due to the variety of organisms studied in these articles and the information provided, different approaches were taken to compare them to the Xenopus data.…”

“…Putative human orthologs are provided as available. The "Notes" column indicates the following: identified as up-regulated in Xenopus tail regeneration in Tazaki et al (2005); identified as down-regulated in Xenopus tail regeneration in Tazaki et al (2005); found differentially expressed in st53/ st59 Xenopus laevis hindlimbs in King et al (2003); and found to be up-regulated in skeletal myogenesis by Summan et al (2003).…”

“…This work has been conducted using many different organisms, including Planaria, fish, frogs, salamanders, mice, and humans (Ishino et al, 2003;King et al, 2003;Summan et al, 2003;Katogi et al, 2004;Swamy et al, 2004;Wolfe et al, 2004;Reddien et al, 2005;Schnapp et al, 2005;Tazaki et al, 2005). Through various approaches (see the Experimental Procedures section), we compared our microarray results to the reported results of eight other published works (Tables 2-5).…”

“…Therefore, we looked into nonepimorphic muscle regeneration outside the context of epimorphic limb regeneration to see if data from this work may shed some light on the issue. The work of Summan et al (2003) focused on gene regulation associated with regenerating skeletal muscle. VIM was identified in that work as up-regulated in skeletal myogenesis and is found in our results to be enriched in the regeneration-incomplete st57 1dPA tissue vs. the regeneration-complete st53 tissue.…”

Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

“…40,41 We suggest that the different characteristics of SASCs from noninjured muscle and injured muscle are related to their modified expression of certain functional genes. Using semiquantitative RT-PCR, we analyzed the expression of several genes related to stem cell multipotency, muscle development, and muscle regeneration to determine whether SASCs from noninjured muscle may express these genes and whether muscle injury may modify expression of these genes in SASCs.…”