AI Article Synopsis

  • The extracellular matrix (ECM) in skeletal muscle is crucial for tissue development, support, and force transmission, and adapts through remodeling in response to mechanical loading.
  • Recent research on older adults indicated that genes important for ECM remodeling, particularly MMP14, were significantly upregulated after 14 weeks of progressive resistance exercise training.
  • A study using single-cell RNA-seq showed that muscle fibers can influence macrophages to enhance MMP14 expression and promote ECM remodeling, establishing a functional connection between muscle activity and immune response in the context of exercise.

Article Abstract

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling processes must occur. In a large cohort of older adults, transcriptomics revealed that genes involved in ECM remodeling, including matrix metalloproteinase 14 (MMP14), were the most upregulated following 14 weeks of progressive resistance exercise training (PRT). Using single-cell RNA-seq, we identified macrophages as a source of Mmp14 in muscle following a hypertrophic exercise stimulus in mice. In vitro contractile activity in myotubes revealed that the gene encoding cytokine leukemia inhibitory factor (LIF) is robustly upregulated and can stimulate Mmp14 expression in macrophages. Functional experiments confirmed that modulation of this muscle cell-macrophage axis facilitated Type I collagen turnover. Finally, changes in LIF expression were significantly correlated with MMP14 expression in humans following 14 weeks of PRT. Our experiments reveal a mechanism whereby muscle fibers influence macrophage behavior to promote ECM remodeling in response to mechanical loading.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875325PMC
http://dx.doi.org/10.1096/fj.202100182RRDOI Listing

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