Glycoprotein 130 improves repressor element‑1 silencing transcription factor‑related axon regenerative capacity in peripheral nerves with aging.

Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep Subsets: MEDLINE

Original Publication: Athens, Greece : D. A. Spandidos

Nerve Regeneration*/genetics ; Axons*/metabolism ; Axons*/physiology ; Aging*/metabolism ; Aging*/genetics ; Repressor Proteins*/metabolism ; Repressor Proteins*/genetics ; Cytokine Receptor gp130*/metabolism ; Cytokine Receptor gp130*/genetics ; Peripheral Nerves*/metabolism ; Peripheral Nerves*/physiology; Animals ; STAT3 Transcription Factor/metabolism ; STAT3 Transcription Factor/genetics ; Mice ; Janus Kinase 1/metabolism ; Janus Kinase 1/genetics ; Signal Transduction ; Male ; GAP-43 Protein/metabolism ; GAP-43 Protein/genetics

Axon regenerative capacity diminishes with aging and differences in the condition of peripheral nerves between young and elderly individuals have been reported. However, the underlying pathology remains unclear. The expression of repressor element‑1 silencing transcription factor (REST) increases with age and is reported to suppress axon regeneration. The present study investigated the pathology and potential treatment of reduced axon regenerative capacity using REST‑regulated cells and a mouse model. This study examined the molecular expression of the janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) pathway, which is involved in growth‑associated protein 43 (GAP43) expression. In REST‑overexpressed (REST‑OE), glycoprotein 130 (GP130), JAK1 and phosphorylated STAT3 (p‑STAT3) expression was decreased compared with the control (GP130, P=0.004; JAK1, P=0.038; pSTAT3, P=0.015). On the other hand, in REST‑low expressed (siREST), GP130, JAK1 and pSTAT3 expression was increased compared with the control (GP130, P=0.004; JAK1, P=0.003; pSTAT3, P=0.033). It suggested that GP130 plays an important role. Therefore, GP130 agonist was administered to REST‑OE and aged mice and resulted in a significant increase in GAP43 expression (REST‑OE: Protein P=0.018, mRNA P=0.040; aged mice: Protein P=0.016, mRNA P=0.013). The results of this study suggest that the pathology of reduction in peripheral nerve axon regenerative capacity is inhibited by age‑related increase in REST expression, which leads to decreased GP130 expression and inhibition of JAK1/STAT3 pathway activity. These findings suggest that regulating GP130 expression may improve axon regenerative capacity by aging.

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Keywords: aging; axon regeneration; glycoprotein 130; janus kinase 1/signal transducer and activator of transcription 3; repressor element 1 silencing transcription factor

0 (RE1-silencing transcription factor)
0 (STAT3 Transcription Factor)
0 (Repressor Proteins)
133483-10-0 (Cytokine Receptor gp130)
EC 2.7.10.2 (Janus Kinase 1)
0 (GAP-43 Protein)

Date Created: 20250307 Date Completed: 20250511 Latest Revision: 20250511

20250512

PMC11920774

10.3892/mmr.2025.13486

40052576