Advisor - Dr. Ralph Sorensen
The role of macrophages in wound healing after muscle injury was studied. This class of macrophages is known as wound healing or M2a macrophages. IL-4 and STAT6 are paracrine hormones responsible for the differentiation of naïve macrophages into wound healing macrophages. Two competing pathways control muscle development. The hypertrophic pathway stimulates muscle growth and is detectable by Arg-1 and YM-1 gene expression, whereas the atrophic pathway controls muscle breakdown and is observable by the expression of MuRF-1 and Atrogin-1 genes. Wound healing macrophages attenuate the atrophic signaling pathway by reducing MuRF-1 and Atrogin-1 expression. qRT-PCR determined that IL-4 mRNA levels increased in a line of mouse muscle cells (H2K) damaged by the cardiotoxin dexamethasone. The addition of IL-4 stimulated macrophages to the H2K cells showed increased expression of Arg-1 and YM-1 genes, markers for the hypertrophic pathway. Immunofluorescence showed increased myogenin protein production in H2K cells in the presence of IL-4 stimulated macrophages. This data shows the importance and time-dependent manner of the signaling events that promote the healing of injured muscle fibers.