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Platelet derived growth factor-CC secreted by M2 macrophages induces alpha-smooth muscle actin expression by dermal

Judith E Glim1, Frank B Niessen, Vincent Everts

  • 1Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. je.glim@vumc.nl

Immunobiology
|November 28, 2012
PubMed

Insights

M2 macrophages promote fibrosis by producing platelet-derived growth factor-CC (PDGF-CC), which drives myofibroblast differentiation in wound healing. This contrasts with M1 macrophages, highlighting a key mechanism in scar formation.

Area of Science:

  • Wound healing research
  • Cell biology
  • Immunology

Background:

  • Dermal wound healing can result in detrimental fibrosis and scarring.
  • Oral mucosa typically heals without significant scarring.
  • Macrophages are key players in wound repair and exhibit heterogeneity, potentially contributing to fibrosis.

Purpose of the Study:

  • To investigate the role of differently activated macrophages in fibrosis.
  • To study the in vitro effect of M1 and M2 macrophages on dermal and gingival fibroblasts.
  • To identify the mechanisms by which macrophages influence myofibroblast differentiation.

Main Methods:

  • Macrophages were differentiated into M1 or M2 phenotypes.
  • Fibroblasts were exposed to macrophages and/or conditioned medium.
  • Myofibroblast differentiation was quantified by α-SMA expression.
  • Receptor expression (CD40/mannose receptor) and cytokine secretion (IL-4/-12) were assessed.
  • Platelet-derived growth factor-CC (PDGF-CC) involvement was confirmed via ELISA, RT-PCR, and blocking experiments.

Main Results:

  • M2 macrophages, but not M1, induced α-SMA expression in both dermal and gingival fibroblasts.
  • Transforming growth factor-β1 (TGF-β1) blocking did not inhibit M2-mediated α-SMA expression.
  • M2 macrophages produced PDGF-CC, which mediated myofibroblast differentiation.
  • PDGF-CC was confirmed as the key mediator through various experimental approaches.

Conclusions:

  • M2 macrophages induce myofibroblast differentiation through PDGF-CC production.
  • PDGF-CC plays a significant, previously unrecognized role in myofibroblast differentiation.
  • Understanding this M2 macrophage-PDGF-CC pathway may offer insights into controlling fibrotic scarring.

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