4.6 Article

Peripheral nerve fibroblasts secrete neurotrophic factors to promote axon growth of motoneurons

Journal

NEURAL REGENERATION RESEARCH
Volume 17, Issue 8, Pages 1833-1840

Publisher

WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.332159

Keywords

brain-derived neurotrophic factor; differential gene expression; F-actin; fibroblasts; motoneurons; mRNA sequencing; neurite outgrowth; peripheral nervous system; beta-actin

Funding

  1. National Key Research and Development Program of China [2017YFA0104703]
  2. National Natural Science Foundation of China [92068112, 31500927, 31870977]
  3. Science and Technology Program of Nantong of China [JC2020035]
  4. Priority Academic Program Development of Jiangsu High Education Institutions (PAPD)

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Peripheral nerve fibroblasts play a critical role in nerve development and regeneration by promoting motoneuron neurite outgrowth. These fibroblasts exhibit different patterns of gene expression compared to cardiac fibroblasts.
Peripheral nerve fibroblasts play a critical role in nerve development and regeneration. Our previous study found that peripheral nerve fibroblasts have different sensory and motor phenotypes. Fibroblasts of different phenotypes can guide the migration of Schwann cells to the same sensory or motor phenotype. In this study, we analyzed the different effects of peripheral nerve-derived fibroblasts and cardiac fibroblasts on motoneurons. Compared with cardiac fibroblasts, peripheral nerve fibroblasts greatly promoted motoneuron neurite outgrowth. Transcriptome analysis results identified 491 genes that were differentially expressed in peripheral nerve fibroblasts and cardiac fibroblasts. Among these, 130 were significantly upregulated in peripheral nerve fibroblasts compared with cardiac fibroblasts. These genes may be involved in axon guidance and neuron projection. Three days after sciatic nerve transection in rats, peripheral nerve fibroblasts accumulated in the proximal and distal nerve stumps, and most expressed brain-derived neurotrophic factor. In vitro, brain-derived neurotrophic factor secreted from peripheral nerve fibroblasts increased the expression of beta-actin and F-actin through the extracellular regulated protein kinase and serine/threonine kinase pathways, and enhanced motoneuron neurite outgrowth. These findings suggest that peripheral nerve fibroblasts and cardiac fibroblasts exhibit different patterns of gene expression. Peripheral nerve fibroblasts can promote motoneuron neurite outgrowth.

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