Exposure to microgravity induces skeletal muscle disorders including atrophy, muscle force decrease, fiber-type shift. Microgravity also contributes to immune-function alterations and modifies microRNAs (miRs) expression. To understand the link between microgravity-induced skeletal muscle atrophy and immune function deregulation, a bioinformatics study was performed. The web platform MiRNet was used for miRs-targets interaction analysis from previous proteomic studies on human soleus (SOL) and vastus lateralis (VL) muscles. We predicted miRs targeting deregulated gene expression following bed rest as a model of microgravity exposure; namely, let-7a-5p, miR-125b-5p for over-expressed genes in SOL and VL; miR-1-3p, miR-125b-5p and miR-1-3p, miR-95-5p for down-expressed genes in VL and SOL. The predicted miRs have important immune functions, exhibiting a significant role on both inflammation and atrophy. Let-7a down-expression leads to proliferation pathways promotion and differentiation pathway inhibition, whereas miR-1-3p over-expression yields anti-proliferative effect, promoting early differentiation. Such conflicting signals could lead to impairment between proliferation and differentiation in skeletal muscles. Moreover, promotion of an M2-like macrophage phenotype (IL-13, IL-10) by let-7a down-regulation and simultaneous promotion of an M1-like macrophage (IL-6, TNF-α) phenotype through the over-expression of EEF2 lead to a deregulation between M1/M2 tuning, that is responsible for a first proinflammatory/proliferative phase followed by an anti-inflammatory pro-myogenic phase during skeletal muscle regeneration after injury. These observations are important to understand the mechanism by which inflammation may play a significant role in skeletal muscle dysfunction in spaceflights, providing new links between immune response and skeletal muscle deregulation, which may be useful to further investigate possible therapeutic intervention.

Skeletal muscle atrophy in simulated microgravity might be triggered by immune-related microRNAs

Teodori L.;
2019

Abstract

Exposure to microgravity induces skeletal muscle disorders including atrophy, muscle force decrease, fiber-type shift. Microgravity also contributes to immune-function alterations and modifies microRNAs (miRs) expression. To understand the link between microgravity-induced skeletal muscle atrophy and immune function deregulation, a bioinformatics study was performed. The web platform MiRNet was used for miRs-targets interaction analysis from previous proteomic studies on human soleus (SOL) and vastus lateralis (VL) muscles. We predicted miRs targeting deregulated gene expression following bed rest as a model of microgravity exposure; namely, let-7a-5p, miR-125b-5p for over-expressed genes in SOL and VL; miR-1-3p, miR-125b-5p and miR-1-3p, miR-95-5p for down-expressed genes in VL and SOL. The predicted miRs have important immune functions, exhibiting a significant role on both inflammation and atrophy. Let-7a down-expression leads to proliferation pathways promotion and differentiation pathway inhibition, whereas miR-1-3p over-expression yields anti-proliferative effect, promoting early differentiation. Such conflicting signals could lead to impairment between proliferation and differentiation in skeletal muscles. Moreover, promotion of an M2-like macrophage phenotype (IL-13, IL-10) by let-7a down-regulation and simultaneous promotion of an M1-like macrophage (IL-6, TNF-α) phenotype through the over-expression of EEF2 lead to a deregulation between M1/M2 tuning, that is responsible for a first proinflammatory/proliferative phase followed by an anti-inflammatory pro-myogenic phase during skeletal muscle regeneration after injury. These observations are important to understand the mechanism by which inflammation may play a significant role in skeletal muscle dysfunction in spaceflights, providing new links between immune response and skeletal muscle deregulation, which may be useful to further investigate possible therapeutic intervention.
Bioinformatics; Immune function deregulation; MiRs prediction; Skeletal muscle atrophy; Space flight; Web-based platform
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12079/53895
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