Uncontrolled muscle fibrosis is the hallmark of Duchenne Muscular Dystrophy (DMD), a destructive genetic disease caused by the mutation in dystrophin gene. However, mdx mice, the mouse model for human DMD, do not exhibit similar fibrotic phenotype in the majority of skeletal muscles except in diaphragm. Here we characterize an important role of transcription factor Stat3 in muscle fibrosis in mdx mice. We found muscle satellite cell (MuSC)-specific Stat3 knockout in mdx mice not only causes self-renewal defects in satellite cells but also significantly enhances the accumulation of fibrotic content. The exacerbated fibrosis in Stat3/mdx double knockout mice (dKO) is accompanied by severe muscle atrophy and infiltration of CD68-positive inflammatory cells and an increase of fibro/adipogen...[ Read more ]

Uncontrolled muscle fibrosis is the hallmark of Duchenne Muscular Dystrophy (DMD), a destructive genetic disease caused by the mutation in dystrophin gene. However, mdx mice, the mouse model for human DMD, do not exhibit similar fibrotic phenotype in the majority of skeletal muscles except in diaphragm. Here we characterize an important role of transcription factor Stat3 in muscle fibrosis in mdx mice. We found muscle satellite cell (MuSC)-specific Stat3 knockout in mdx mice not only causes self-renewal defects in satellite cells but also significantly enhances the accumulation of fibrotic content. The exacerbated fibrosis in Stat3/mdx double knockout mice (dKO) is accompanied by severe muscle atrophy and infiltration of CD68-positive inflammatory cells and an increase of fibro/adipogenic progenitors (FAPs). Interestingly, FAPs isolated from dKO mice are less prone to adipogenic differentiation and exhibit more fibrogenic features in vitro. This suggests a possible cross-talk between Stat3-null MuSCs and FAPs which promotes a fibrogenic program via a yet unknown mechanism in mdx mice. We are conducting more experiments to validate this hypothesis.