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Changes of pro-inflammatory and anti-inflammatory macrophages after peripheral nerve injury

Fuchao Zhang1, Yang Miao2, Qianyan Liu1

  • 1Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University Nantong Jiangsu 226001 China hejh@ntu.edu.cn.

RSC Advances
|May 6, 2022
PubMed

Insights

Peripheral nerve injury involves dynamic changes in pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. This study reveals M1 macrophages are consistently involved, while M2 macrophages dominate later stages, impacting nerve regeneration.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Regenerative Medicine

Background:

  • Macrophages are crucial immune cells responding to peripheral nerve injury.
  • Different macrophage subtypes (M1 and M2) have distinct roles in nerve repair.
  • The temporal dynamics of M1 and M2 macrophages post-injury remain largely uncharacterized.

Purpose of the Study:

  • To investigate the dynamic expression profiles of M1 and M2 macrophage marker genes after rat sciatic nerve injury.
  • To explore the role of specific microRNAs (miRNAs) in macrophage polarization during nerve regeneration.
  • To elucidate the cellular and molecular mechanisms underlying microenvironment reconstruction post-nerve injury.

Main Methods:

  • RNA sequencing was employed to analyze gene expression in sciatic nerve stumps and dorsal root ganglions (DRGs).
  • Dynamic expression levels of M1 (CD38, Gpr18) and M2 (Egr2, Myc) macrophage markers were measured.
  • Expression patterns of M1 macrophage-inducing miRNAs (miR-18a, miR-19b, miR-21, miR-29a, miR-29b) were analyzed.

Main Results:

  • Macrophage marker gene expression was significantly upregulated in injured sciatic nerve stumps compared to DRGs.
  • M1 macrophages showed high involvement throughout all tested time points, whereas M2 macrophages appeared more prominent in later phases.
  • Several miRNAs, including miR-18a, miR-19b, miR-21, miR-29a, and miR-29b, were elevated in the injured nerve stump, potentially targeting genes like Pten to mediate macrophage polarization.

Conclusions:

  • This study reveals distinct temporal patterns of M1 and M2 macrophage involvement following peripheral nerve injury.
  • Up-regulated miRNAs may play a key role in regulating macrophage polarization and nerve regeneration.
  • Findings provide a deeper understanding of the molecular basis of microenvironment remodeling after nerve injury.

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