Collagen VI regulates peripheral nerve regeneration by modulating macrophage recruitment and polarization

Peiwen Chen, Matilde Cescon, Gaia Zuccolotto, Lucilla Nobbio, Cristina Colombelli, Monica Filaferro, Giovanni Vitale, M. Laura Feltri, Paolo Bonaldo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Macrophages contribute to peripheral nerve regeneration and produce collagen VI, an extracellular matrix protein involved in nerve function. Here, we show that collagen VI is critical for macrophage migration and polarization during peripheral nerve regeneration. Nerve injury induces a robust upregulation of collagen VI, whereas lack of collagen VI in Col6a1−/− mice delays peripheral nerve regeneration. In vitro studies demonstrated that collagen VI promotes macrophage migration and polarization via AKT and PKA pathways. Col6a1−/− macrophages exhibit impaired migration abilities and reduced antiinflammatory (M2) phenotype polarization, but are prone to skewing toward the proinflammatory (M1) phenotype. In vivo, macrophage recruitment and M2 polarization are impaired in Col6a1−/− mice after nerve injury. The delayed nerve regeneration of Col6a1−/− mice is induced by macrophage deficits and rejuvenated by transplantation of wild-type bone marrow cells. These results identify collagen VI as a novel regulator for peripheral nerve regeneration by modulating macrophage function.

Original languageEnglish (US)
Pages (from-to)97-113
Number of pages17
JournalActa Neuropathologica
Issue number1
StatePublished - Jan 1 2015
Externally publishedYes


  • Collagen VI
  • Macrophage
  • Migration
  • Nerve regeneration
  • Peripheral nerve
  • Polarization

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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