Repeated mechanical stress causes injuries in the adult skeletal muscle that need to be repaired. Although muscle regeneration is a highly efficient process, it fails in some pathological conditions, compromising tissue functionality. This may be caused by aberrant cell-cell communication, resulting in the deposition of fibrotic and adipose infiltrates. Here, we investigate in vivo changes in the profile of skeletal muscle secretome during the regeneration process to suggest new targetable regulatory circuits whose failure may lead to tissue degeneration in pathological conditions. We describe the kinetic variation of expression levels of 76 secreted proteins during the regeneration process. In addition, we profile the gene expression of immune cells, endothelial cells, satellite cells, and fibro-adipogenic progenitors. This analysis allowed us to annotate each cell-type with the cytokines and receptors they have the potential to synthetize, thus making it possible to draw a cell-cell interaction map. We next selected 12 cytokines whose receptors are expressed in FAPs and tested their ability to modulate FAP adipogenesis and proliferation. We observed that IL1 alpha and IL1 beta potently inhibit FAP adipogenesis, while EGF and BTC notably promote FAP proliferation. In addition, we characterized the cross-talk mediated by extracellular vesicles (EVs). We first monitored the modulation of muscle EV cargo during tissue regeneration. Using a single-vesicle flow cytometry approach, we observed that EVs differentially affect the uptake of RNA and proteins into their lumen. We also investigated the EV capability to interact with SCs and FAPs and to modulate their proliferation and differentiation. We conclude that both cytokines and EVs secreted during muscle regeneration have the potential to modulate adipogenic differentiation of FAPs. The results of our approach provide a system-wide picture of mechanisms that control cell fate during the regeneration process in the muscle niche.

Vumbaca, S., Giuliani, G., Fiorentini, V., Tortolici, F., Perpetuini, A.c., Riccio, F., et al. (2021). Characterization of the skeletal muscle secretome reveals a role for extracellular vesicles and il1α/il1β in restricting fibro/adipogenic progenitor adipogenesis. BIOMOLECULES, 11(8), 1171 [10.3390/biom11081171].

Characterization of the skeletal muscle secretome reveals a role for extracellular vesicles and il1α/il1β in restricting fibro/adipogenic progenitor adipogenesis

Gargioli C.;Fuoco C.;Castagnoli L.;Cesareni G.
2021-01-01

Abstract

Repeated mechanical stress causes injuries in the adult skeletal muscle that need to be repaired. Although muscle regeneration is a highly efficient process, it fails in some pathological conditions, compromising tissue functionality. This may be caused by aberrant cell-cell communication, resulting in the deposition of fibrotic and adipose infiltrates. Here, we investigate in vivo changes in the profile of skeletal muscle secretome during the regeneration process to suggest new targetable regulatory circuits whose failure may lead to tissue degeneration in pathological conditions. We describe the kinetic variation of expression levels of 76 secreted proteins during the regeneration process. In addition, we profile the gene expression of immune cells, endothelial cells, satellite cells, and fibro-adipogenic progenitors. This analysis allowed us to annotate each cell-type with the cytokines and receptors they have the potential to synthetize, thus making it possible to draw a cell-cell interaction map. We next selected 12 cytokines whose receptors are expressed in FAPs and tested their ability to modulate FAP adipogenesis and proliferation. We observed that IL1 alpha and IL1 beta potently inhibit FAP adipogenesis, while EGF and BTC notably promote FAP proliferation. In addition, we characterized the cross-talk mediated by extracellular vesicles (EVs). We first monitored the modulation of muscle EV cargo during tissue regeneration. Using a single-vesicle flow cytometry approach, we observed that EVs differentially affect the uptake of RNA and proteins into their lumen. We also investigated the EV capability to interact with SCs and FAPs and to modulate their proliferation and differentiation. We conclude that both cytokines and EVs secreted during muscle regeneration have the potential to modulate adipogenic differentiation of FAPs. The results of our approach provide a system-wide picture of mechanisms that control cell fate during the regeneration process in the muscle niche.
2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13 - BIOLOGIA APPLICATA
English
adipogenesis
cytokine
extracellular vesicles
faps
muscle regeneration
secretome
Adipocytes
Adipogenesis
Animals
Cardiotoxins
Cell Communication
Cell Differentiation
Cell Proliferation
Cytokines
Endothelial Cells
Extracellular Vesicles
Fibroblasts
Gene Expression Profiling
Gene Expression Regulation
Interleukin-1alpha
Interleukin-1beta
Mice
Mice, Inbred C57BL
Muscle, Skeletal
Myoblasts
Proteome
Regeneration
Stem Cells
Vumbaca, S., Giuliani, G., Fiorentini, V., Tortolici, F., Perpetuini, A.c., Riccio, F., et al. (2021). Characterization of the skeletal muscle secretome reveals a role for extracellular vesicles and il1α/il1β in restricting fibro/adipogenic progenitor adipogenesis. BIOMOLECULES, 11(8), 1171 [10.3390/biom11081171].
Vumbaca, S; Giuliani, G; Fiorentini, V; Tortolici, F; Perpetuini, Ac; Riccio, F; Sennato, S; Gargioli, C; Fuoco, C; Castagnoli, L; Cesareni, G...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/295645
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