title: Collagen VI regulates peripheral nerve regeneration by modulating macrophage recruitment and polarization.
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.
authors.affiliation: Department of Molecular Medicine, University of Padua, Via Ugo Bassi 58/B, 35131, Padua, Italy.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Chen
authors.forename: Matilde
authors.initials: M
authors.lastname: Cescon
authors.forename: Gaia
authors.initials: G
authors.lastname: Zuccolotto
authors.forename: Lucilla
authors.initials: L
authors.lastname: Nobbio
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombelli
authors.forename: Monica
authors.initials: M
authors.lastname: Filaferro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology*
chemical_list: C540085:Col6a1 protein, mouse; D024142:Collagen Type VI