Transgenic Schwann cells overexpressing POU6F1 promote sciatic nerve regeneration within acellular nerve allografts

Abstract

Objective. Acellular nerve allograft (ANA) is an effective surgical approach used to bridge the sciatic nerve gap. The molecular regulators of post-surgical recovery are not well-known. Here, we explored the effect of transgenic Schwann cells (SCs) overexpressing POU domain class 6, transcription factor 1 (POU6F1) on sciatic nerve regeneration within acellular nerve allografts. we explored the functions of POU6F1 in nerve regeneration by using a cell model of H2O2-induced SCs injury and transplanting SCs overexpressing POU6F1 into ANA to repair sciatic nerve gaps. Approach. Using RNA-seq, Protein-Protein Interaction network analysis, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we identified a highly and differentially expressed transcription factor, POU6F1, following ANA treatment of sciatic nerve gap. Expressing a high degree of connectivity, POU6F1 was predicted to play a role in peripheral nervous system myelination. Main results. To test the role of POU6F1 in nerve regeneration after ANA, we infected SCs with adeno-associated virus (AAV) – POU6F1, demonstrating that POU6F1 overexpression promotes proliferation, anti-apoptosis, and migration of SCs in vitro. We also found that POU6F1 significantly upregulated JNK1/2 and c-Jun phosphorylation and that selective JNK1/2 inhibition attenuated the effects of POU6F1 on proliferation, survival, migration, and JNK1/2 and c-Jun phosphorylation. The direct interaction of POU6F1 and activated JNK1/2 was subsequently confirmed by co-immunoprecipitation. In rat sciatic nerve injury model with a 10 mm gap, we confirmed the pattern of POU6F1 upregulation and co-localization with transplanted SCs. ANAs loaded with POU6F1-overexpressing SCs demonstrated the enhanced survival of transplanted SCs, axonal regeneration, myelination, and functional motor recovery compared to the ANA group loaded by SCs-only in line with in vitro findings. Significance. This study identifies POU6F1 as a novel regulator of post-injury sciatic nerve repair, acting through JNK/c-Jun signaling in SCs to optimize therapeutic outcomes in the ANA surgical approach.

Significance of platelet adhesion-related genes in colon cancer based on non-negative matrix factorization-based clustering algorithm

“…The analysis revealed that 10 hub genes were enriched in POU6F1, which is a member of the POU factor family of transcription factors. 46 Interestingly, in the present study, POU6F1 was identified to have a low expression in tumor tissues, when compared to normal tissues. Another study reported that downregulation of POU6F1 in lung adenocarcinoma (LUAD) is associated with poor prognosis.…”

An experimental and numerical study of the microstructural and biomechanical properties of human peripheral nerve endoneurium for the design of tissue scaffolds

“…The preserved ECM components create a milieu similar to peripheral nerve tissue for schwann cell adhesion and proliferation ( Su et al, 2022 ). Some studies show that removing the factors inhibiting axonal growth from ECM will enhance the effect of acellular nerve allograft (ANA) ( Li et al, 2022 ). Our team developed a ANA product approved by the Chinese Food and Drug Administration (CFDA) (Guangzhou Zhongda Medical Devices Company, Guangzhou, Guangdong Province, China; Approval No.…”