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Cellular senescence and proliferation are essential for wound healing and tissue remodeling. However, senescence-proliferation cell fate after peripheral nerve injury has not been clearly revealed. Here, post-injury gene expression patterns in rat sciatic nerve stumps (SRP113121) and L4–5 dorsal root ganglia (SRP200823) obtained from the National Center for Biotechnology Information were analyzed to decipher cellular senescence and proliferation-associated genetic changes. We first constructed a rat sciatic nerve crush model. Then, β-galactosidase activities were determined to indicate the existence of cellular senescence in the injured sciatic nerve. Ki67 and EdU immunostaining was performed to indicate cellular proliferation in the injured sciatic nerve. Both cellular senescence and proliferation were less vigorous in the dorsal root ganglia than in sciatic nerve stumps. These results reveal the dynamic changes of injury-induced cellular senescence and proliferation from both genetic and morphological aspects, and thus extend our understanding of the biological processes following peripheral nerve injury. The study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20190226-001) on February 26, 2019.

The regenerative capacity of peripheral nerves is limited after nerve injury. A number of growth factors modulate many cellular behaviors, such as proliferation and migration, and may contribute to nerve repair and regeneration. Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing. Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3, 9 hours, 1, 4, or 7 days after nerve crush, compared with the 0 hour control. Thirty-six rat models of sciatic nerve crush injury were prepared as described previously. Then, they were divided into six groups to measure the expression changes of representative genes at 0, 3, 9 hours, 1, 4 or 7 days post crush. Our current study measured the expression levels of representative upstream growth factors, including nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor 2 and amphiregulin genes, and explored critical signaling pathways and biological process through bioinformatic analysis. Our data revealed that many of these dysregulated upstream growth factors, including nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor 2 and amphiregulin, participated in tissue remodeling and axon growth-related biological processes Therefore, the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury. Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves. All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals, China (approval No. 20170302-017) on March 2, 2017.