RRC ID 70683
Author Matsui Y, Kadoya K, Nagano Y, Endo T, Hara M, Matsumae G, Suzuki T, Yamamoto Y, Terkawi MA, Iwasaki N.
Title IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.
Journal Cell Mol Life Sci
Abstract Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.
Volume 79(6)
Pages 289
Published 2022-5-10
DOI 10.1007/s00018-022-04310-5
PII 10.1007/s00018-022-04310-5
PMID 35536429
IF 6.496
Rats LEW-Tg(CAG-EGFP)1Ys (StrainID=647)