STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats
Objective To study the effect of STAT3 over-expression-mediated A2 astrocyte polarization on type 1 diabetic mellitus(T1DM)peripheral neuropathy. Methods STAT3 over-expression virus was intrathecally injected into type 1 diabetic rats with painful diabetic neuropathy(PDN). The rats were divided into...
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| Main Author: | |
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| Format: | Article |
| Language: | Chinese |
| Published: |
Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
2025-07-01
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| Series: | Jichu yixue yu linchuang |
| Subjects: | |
| Online Access: | https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-889.pdf |
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| Summary: | Objective To study the effect of STAT3 over-expression-mediated A2 astrocyte polarization on type 1 diabetic mellitus(T1DM)peripheral neuropathy. Methods STAT3 over-expression virus was intrathecally injected into type 1 diabetic rats with painful diabetic neuropathy(PDN). The rats were divided into four groups: control group, T1DM group, T1DM + vector group, and T1DM + STAT3 OE group. Paw withdrawal threshold and paw withdrawal latency were measured. Flow cytometry and RT-qPCR were used to sort astrocytes and determine the phenotype of reactive astrocytes. Immune-fluorescence staining microscopy was performed to observe the changes of A2 phenotype astrocytes in the spinal dorsal horn of each group. Results Compared to the control group, the mechanical (P＜0.001) and heat thresholds (P＜0.05) were significantly reduced in the T1DM group. The mechanical threshold was significantly increased in the T1DM+STAT3 OE group as compared to that in the T1DM group(P＜0.001). Histolgical analysis showed degenerative pathological changes of spinal dorsal horn astrocytes in the T1DM group. Astrocytes in the T1DM+STAT3 OE group were activated and polarized toward the A2 phenotype. Conclusions The STAT3 pathway in the spinal dorsal horn astrocytes of rats with type 1 diabetic neuropathy is impaired. Restoring STAT3 expression promotes activation of astrocyte proliferation, activation, and polarization toward the A2 phenotype, thereby alleviating diabetic neuropathic pain. |
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| ISSN: | 1001-6325 |