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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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 |
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| Online Access: | https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-889.pdf |
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| author | FAN Tingting, LI Huili, GUO Ruijuan, MA Danxu, WANG Yun |
| author_facet | FAN Tingting, LI Huili, GUO Ruijuan, MA Danxu, WANG Yun |
| author_sort | FAN Tingting, LI Huili, GUO Ruijuan, MA Danxu, WANG Yun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8e49fe5ce2ba49b6875f52f0a92e28a1 |
| institution | Matheson Library |
| issn | 1001-6325 |
| language | zho |
| publishDate | 2025-07-01 |
| publisher | Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. |
| record_format | Article |
| series | Jichu yixue yu linchuang |
| spelling | doaj-art-8e49fe5ce2ba49b6875f52f0a92e28a12025-07-01T06:28:03ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252025-07-0145788989610.16352/j.issn.1001-6325.2025.07.0889STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic ratsFAN Tingting, LI Huili, GUO Ruijuan, MA Danxu, WANG Yun0Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaObjective 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.https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-889.pdftype 1 diabetic mellitus (t1dm)|painful diabetic neuropathy (pdn)|signal transducer and activator of transcription 3 (stat3)|a2 phenotype reactive astrocytes |
| spellingShingle | FAN Tingting, LI Huili, GUO Ruijuan, MA Danxu, WANG Yun STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats Jichu yixue yu linchuang type 1 diabetic mellitus (t1dm)|painful diabetic neuropathy (pdn)|signal transducer and activator of transcription 3 (stat3)|a2 phenotype reactive astrocytes |
| title | STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats |
| title_full | STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats |
| title_fullStr | STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats |
| title_full_unstemmed | STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats |
| title_short | STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats |
| title_sort | stat3 mediated polarization of a2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats |
| topic | type 1 diabetic mellitus (t1dm)|painful diabetic neuropathy (pdn)|signal transducer and activator of transcription 3 (stat3)|a2 phenotype reactive astrocytes |
| url | https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-889.pdf |
| work_keys_str_mv | AT fantingtinglihuiliguoruijuanmadanxuwangyun stat3mediatedpolarizationofa2phenotypeastrocytesalleviatespainfuldiabeticperipheralneuropathyintype1diabeticrats |