G) Quantification of percentage of Tcf4+ cells that also express αSMA in SC-WT and SC-Dep skeletal muscle at baseline (sham), SA1 and SA2. † denotes significant difference from sham p <0.05 (N = 5 mice/group). F) Quantification of Tcf4+ fibrogenic cells in SC-WT and SC-Dep skeletal muscle at baseline (sham), SA1 and SA2. The orange arrowhead in B-E identifies a rare Tcf4+/αSMA+ myofibroblast. E) Merged image of Tcf4, αSMA and DAPI staining in the SC-Dep muscle cross-section. Blood vessels (white arrows) are strongly αSMA+, serving as a positive control. Representative images of a SC-Dep muscle cross-section at SA1 illustrating immunohistochemical identification of (B) Tcf4+ (green) (C) α smooth muscle actin (αSMA) + (orange) cells. Following tamoxifen or vehicle treatment and a two week washout, plantaris muscle was mechanically overloaded using synergist ablation for either one (SA1) or two (SA2) weeks.

Pax7 collagen exosomes extracellular matrix fibrosis hypertrophy microRNA muscle muscle progenitor cells satellite cells.Ĭopyright © 2017 Elsevier Inc. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers.

Kirby s kjar mdm