Sensory and motor fibroblasts have different protein expression patterns and exert different growth promoting effects on sensory and motor neurons

Functional reconstruction after peripheral nerve injury depends on the ability of the regenerated sensory and motor axons to re-innervate the suitable target organs. Therefore, it is essential to explore the cellular mecha-nisms of peripheral nerve-specific regeneration. In a previous study, we found that sensory and motor fibroblasts can guide Schwann cells to migrate towards the same phenotype. In the present paper, we analyzed the different effects of sensory and motor fibroblasts on sensory or motor neurons. The fibroblasts and neurons co-culture assay showed that compared with motor fibroblasts, sensory fibroblasts promote the neurite outgrowth of sen-sory neurons on a larger scale, and vice versa. Furthermore, a higher proportion of sensory or motor fibroblasts migrated towards their respective (sensory or motor) neurons. Meanwhile, a comparative proteomic approach was applied to obtain the protein expression profiles of sensory and motor fibroblasts. Among a total of 2597 overlapping proteins identified, we counted 148 differentially expressed items, of those 116 had a significantly higher expression in sensory fibroblasts, and 32 had a significantly greater expression in motor fibroblasts. Functional categorization revealed that differentially expressed proteins were involved in regeneration, axon guidance and cytoskeleton organization, all of which might play a critical role in peripheral nerve-specific regeneration. After nerve crush injury, ITB1 protein expression decreased significantly in motor nerves and increased in sensory nerves. In vitro, ITB1 significantly promoted axonal regeneration of sensory neurons, but had no significant effect on motor neurons. Overall, sensory and motor fibroblasts express different proteins and exert different growth promoting effects on sensory and motor neurons. This comparative proteomic database of sensory and motor fibroblasts could provide future directions for in-depth research on peripheral nerve-specific regeneration. Data are available via ProteomeXchange with identifier PXD034827.

Automated summary

Functional reconstruction after peripheral nerve injury relies on the regeneration and re-innervation ability of sensory and motor axons. This study explores the cellular mechanisms of peripheral nerve-specific regeneration. It was found that sensory and motor fibroblasts have different effects on sensory and motor neurons, and the protein expression profiles of these fibroblasts are distinct. These findings provide potential directions for future research on peripheral nerve-specific regeneration.