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Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and contribute to the generation of a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, we find that FOSL1, a AP-1 member that encodes transcription factor FOS Like 1, is highly expressed at the injured sites following peripheral nerve crush. Interfering FOSL1 decreases the proliferation rate and migration ability of Schwann cells, leading to impaired nerve regeneration. Mechanism investigations demonstrate that FOSL1 regulates Schwann cell proliferation and migration by directly binding to the promoter of EPH Receptor B2 (EPHB2) and promoting EPHB2 transcription. Collectively, our findings reveal the essential roles of FOSL1 in regulating the activation of Schwann cells and indicate that FOSL1 can be targeted as a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves.

Peripheral nerves have limited regeneration ability following nerve injury. Applying growth factors with neurotrophic roles is beneficial for accelerating peripheral nerve regeneration. Here we show that after rat sciatic nerve injury, growth factor amphiregulin (AREG) is upregulated in Schwann cells of sciatic nerves. Elevated AREG stimulates the proliferation and migration of Schwann cells by activating ERK1/2 cascade. Schwann cell-secreted AREG further facilitates the outgrowth of neurites and the elongation of injured axons. Administration of AREG to injured sciatic nerves stimulates the proliferation of Schwann cells to replace lost cell population, encourages the migration of Schwann cells to form cell cords, and facilitates the regrowth of axons. Overall, our results identify AREG as an important neurotrophic factor and thus provide a promising therapeutic avenue towards peripheral nerve injury.

UNASSIGNED: Silkworm products were first used by physicians more than 8500 years ago, in the early Neolithic period. In Persian medicine, silkworm extract has several uses for treating and preventing neurological, cardiac, and liver diseases. Mature silkworms (Bombyx mori) and their pupae contain a variety of growth factors and proteins that can be used in many repair processes, including nerve regeneration.
UNASSIGNED: The study aimed to evaluate the effects of mature silkworm (Bombyx mori), and silkworm pupae extract on Schwann cell proliferation and axon growth.
UNASSIGNED: Silkworm (Bombyx mori) and silkworm pupae extracts were prepared. Then, the concentration and type of amino acids and proteins in the extracts were evaluated by Bradford assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and liquid chromatograph-mass spectrometer (LC-MS/MS). Also, the regenerative potential of extracts for improving Schwann cell proliferation and axon growth was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, electron microscopy, and NeuroFilament-200 (NF-200) immunostaining.
UNASSIGNED: According to the results of the Bradford test, the total protein content of pupae extract was almost twice that of mature worm extract. Also, SDS-PAGE analysis revealed numerous proteins and growth factors, such as bombyrin and laminin, in extracts that are involved in the repair of the nervous system. In accordance with Bradford\'s results, the evaluation of extracts using LC-MS/MS revealed that the number of amino acids in pupae extract was higher than in mature silkworm extract. It was found that the proliferation of Schwann cells at a concentration of 0.25 mg/mL in both extracts was higher than the concentrations of 0.01 and 0.05 mg/mL. When using both extracts on dorsal root ganglion (DRGs), an increase in length and number was observed in axons.
UNASSIGNED: The findings of this study demonstrated that extracts obtained from silkworms, especially pupae, can play an effective role in Schwann cell proliferation and axonal growth, which can be strong evidence for nerve regeneration, and, consequently, repairing peripheral nerve damage.

A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.

The object of this study was to explore the effect of rapamycin regulating the proliferation of Schwann cells through activating the extracellular signal-regulated kinase (ERK) signaling pathway on rats with spinal cord injury (SCI). The rat Schwann cells were cultured and divided into solvent (DMSO) group, rapamycin (Rapa) group (1.5 nM, 3.0 nM, 6.0 nM, 12.0 nM, 24.0 nM and 48.0 nM), and Rapa + ERK inhibitor (PD98059) group (40 mM). The proliferation of Schwann cells was detected by MTS. Western blot was used to evaluate the expression of ERK and p-ERK protein. Moreover, the spinal cord compression injury rat model was established, and the rats were divided into normal control group, SCI group and Schwann cell transplantation group. The animal experiment ended 7 weeks after Schwann cells had been injected every day into the injured rats. In the second animal experiment, the rats were divided into DMSO group, Rapa group and Rapa + PD98059 group. The motor recovery of rats was evaluated using the Basso-Beattie-Bresnahan (BBB) score every week, and the proliferation of Schwann cells at the site of SCI was detected using immunohistochemistry. It was verified that lowdose rapamycin (1.5 nM) could significantly promote the proliferation of Schwann cells cultured in vitro (P<0.001), most significantly at 48 h. Rapamycin could activate the ERK signaling pathway. The results of the first animal experiment showed that the BBB score in Schwann cell transplantation group rose with time compared with that in SCI group (P<0.05). The BBB score was obviously increased in Rapa group compared with that in DMSO group and Rapa + PD98059 group (P<0.05). According to the results of Ki67 immunohistochemistry, the proliferation ability of Schwann cells at the site of SCI was remarkably stronger than that in the other two groups. Rapamycin regulates the proliferation of Schwann cells through the ERK signaling pathway. The proliferation of Schwann cells can effectively repair the damaged nerve cells and neurological function in SCI rats.