TERT Promotes Reactive Astrocytes Proliferation and Differentiation Through the Wnt/β-Catenin Pathway and Improves Spinal Cord Injury.

Spinal cord injury (SCI) is a serious neurological disorder for which there is currently no effective treatment. Telomerase reverse transcriptase (TERT), as the catalytic subunit of telomerase, is closely related to the proliferation and differentiation of astrocytes. This study aims to explore the mechanism of the TERT gene in promoting SCI repair and regeneration by inducing reactive astrocytes (RAs) and its potential application as a therapeutic target. First, the RAs model of TERT gene overexpression was constructed using a lentiviral vector, and its efficiency was verified using qRT-PCR and Western blotting. The effect of TERT expression on the proliferation and apoptosis of RAs was detected using CCK8 and flow cytometry assays. Subsequently, immunofluorescence and Western blotting were used to detect changes in the expression of proteins, such as NFL, Nestin, NSE, and GFAP, as well as their protein interactions with downstream pathways, such as GSK-3β, Klf4, and β-catenin, to further explore the specific mechanism of the TERT gene in SCI regeneration and repair. CCK8 assay showed that the survival rate of RAs increased with the upregulation of TERT expression. Flow cytometry assay showed that TERT expression was negatively correlated with the apoptosis rate of RAs. Immunofluorescence showed that the expression of proteins, such as NFL, GFAP, and Nestin, increased with the upregulation of TERT expression, suggesting that TERT upregulation is involved in the proliferation and neural differentiation of RAs. Furthermore, western blotting showed that after TERT expression was upregulated, GSK-3β expression was significantly downregulated, whereas Klf4, β-catenin, Nestin, and NSE were significantly upregulated compared with the control group. Upregulation of TERT expression enhances the proliferation of RAs and inhibits their apoptosis. The expression level of TERT is positively correlated with the proliferation and neural differentiation of RAs. In addition, these findings suggest that TERT can promote the proliferation and differentiation of RAs by regulating the Wnt/β-catenin pathway, demonstrating the potential of TERT as a therapeutic target for SCI.