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

被引：128

作者：

Chen, Peiwen ^{[1
]}

Cescon, Matilde ^{[1
]}

Zuccolotto, Gaia ^{[2
]}

Nobbio, Lucilla ^{[3
]}

Colombelli, Cristina ^{[4
]}

Filaferro, Monica ^{[5
]}

Vitale, Giovanni ^{[6
]}

Feltri, M. Laura ^{[4
,7
]}

Bonaldo, Paolo ^{[1
]}

机构：

[1] Univ Padua, Dept Mol Med, I-35131 Padua, Italy

[2] Univ Padua, Dept Surg Oncol & Gastroenterol, I-35128 Padua, Italy

[3] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Mother &, I-16132 Genoa, Italy

[4] Ist Sci San Raffaele, Dept Genet & Cell Biol, I-20132 Milan, Italy

[5] Univ Modena & Reggio Emilia, Pharmacol Sect, Dept Biomed Metab Sci & Neurosci, I-41125 Modena, Italy

[6] Univ Modena & Reggio Emilia, Pharmacol Sect, Dept Life Sci, I-41125 Modena, Italy

[7] SUNY Buffalo, Hunter James Kelly Res Inst, Buffalo, NY 14203 USA

来源：

ACTA NEUROPATHOLOGICA | 2015年 / 129卷 / 01期

关键词：

Collagen VI; Nerve regeneration; Macrophage; Migration; Polarization; Peripheral nerve; MONOCYTE CHEMOATTRACTANT PROTEIN-1; PROMOTE AXONAL REGENERATION; WALLERIAN DEGENERATION; ALTERNATIVE ACTIVATION; FUNCTIONAL RECOVERY; TUMOR ANGIOGENESIS; MYELIN DEBRIS; MICE; INJURY; CELLS;

D O I：

10.1007/s00401-014-1369-9

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：97 / 113

页数：17

共 52 条

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