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01-01-2015 | Original Paper

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

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

Published in: Acta Neuropathologica | Issue 1/2015

Abstract

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.

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Title: Collagen VI regulates peripheral nerve regeneration by modulating macrophage recruitment and polarization
Authors: Peiwen Chen
Matilde Cescon
Gaia Zuccolotto
Lucilla Nobbio
Cristina Colombelli
Monica Filaferro
Giovanni Vitale
M. Laura Feltri
Paolo Bonaldo
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 1/2015
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-014-1369-9

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

Abstract

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