A population of normally quiescent satellite cells that reside adjacent to skeletal muscle fibers is responsible for muscle regeneration following injury. Activation of these satellite cells and the regeneration of damaged muscle may be dependent on macrophage infiltration. Preliminary studies of mice with altered inflammation demonstrated delays in muscle regeneration and increased adiposity within muscle following injury. Increased fat deposition within and between skeletal muscle fibers also occurs in aging due to impairments in muscle regeneration. Factors present in the healing microenvironment during injury and altered inflammation may direct the differentiation fate of satellite cells to adipocyte rather than muscle by shifting the expression of specific transcription factors. The proposed studies will determine the contribution of the healing microenvironment and transcriptional signaling events that direct adipogenic rather than myogenic differentiation of satellite cells.
The specific aims are to: 1) determine the expression levels of myogenic and adipogenic transcription factors to uncover changes in transcriptional events leading to the altered muscle regeneration observed in CCR2 -/- mice following injury, 2) verify that the healing microenvironment contributes to altered muscle regeneration using in vitro satellite cell culture and 3) demonstrate that conditions which favor the upregulation of adipogenic vs myogenic transcription factors promote an adipogenic or myogenic phenotype, respectively, in regenerating muscle.
| Shireman, Paula K; Contreras-Shannon, Veronica; Ochoa, Oscar et al. (2007) MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration. J Leukoc Biol 81:775-85 |
| Shireman, Paula K; Contreras-Shannon, Veronica; Reyes-Reyna, Sara M et al. (2006) MCP-1 parallels inflammatory and regenerative responses in ischemic muscle. J Surg Res 134:145-57 |
