Activation of skeletal muscle–resident glial cells upon nerve injury

JCI Insight, 2021 · DOI: https://doi.org/10.1172/jci.insight.143469 · Published: April 8, 2021

Simple Explanation

Skeletal muscle contains various types of cells that help maintain its health and respond to injuries. Among these are muscle stem cells and other resident cells. When a nerve is damaged, it can affect the muscle. This study identifies a type of glial cell in muscle that becomes active when nerve damage occurs, potentially aiding in the repair process. In a mouse model of ALS, these glial cells show impaired function, suggesting they may play a role in the disease's progression by not properly supporting the nerve-muscle connection.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Muscle-resident glial cells, identified by Itga7 expression, are activated by nerve injury and express neurotrophic genes like Ngfr, Tnc and Gdnf.
2
These glial cells are distinct from muscle satellite cells (MuSCs) and smooth muscle mesenchymal cells (SMMCs), showing a unique gene expression profile.
3
In a mouse model of ALS, muscle glial cells show impaired neurotrophic activity, suggesting a role in disease progression.

Research Summary

This study identifies Itga7-expressing muscle-resident glial cells that are activated by loss of neuromuscular junction (NMJ) integrity. Upon activation, muscle glial–derived progenies expressed neurotrophic genes, including nerve growth factor receptor, which enables their isolation by FACS. In a mouse model of ALS, muscle glial cells steadily increased over the course of the disease but exhibited an impaired neurotrophic activity, suggesting that pathogenic activation of glial cells may be implicated in ALS progression.

Practical Implications

Therapeutic Targets

Targeting muscle glial cells could be a novel therapeutic strategy for counteracting muscle denervation.

NMJ Repair Enhancement

Understanding the role of muscle glial cells in NMJ repair may lead to new approaches for treating nerve injuries.

ALS Pathogenesis

Defective activity of muscle glial cells could contribute to the pathogenesis of neurodegenerative diseases, such as ALS.

Study Limitations

1
The study primarily uses mouse models, and findings may not directly translate to humans.
2
The precise mechanisms by which muscle glial cells contribute to NMJ repair require further investigation.
3
Further research is needed to determine the potential for pharmacological manipulation of muscle glial cells in neurodegenerative disorders.

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