Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury
The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2025-11-01
|
| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-23-01256 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556359562133504 |
|---|---|
| author | Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng |
| author_facet | Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng |
| author_sort | Ziwei Fan |
| collection | DOAJ |
| description | The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress–related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia–derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype. |
| format | Article |
| id | doaj-art-73c5a9401ef14632b4faf96d975a2196 |
| institution | Kabale University |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-73c5a9401ef14632b4faf96d975a21962025-01-07T09:49:28ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-11-0120113287330110.4103/NRR.NRR-D-23-01256Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injuryZiwei FanMengxian JiaJian ZhouZhoule ZhuYumin WuXiaowu LinYiming QianJiashu LianXin HuaJianhong DongZheyu FangYuqing LiuSibing ChenXiumin XueJuanqing YueMinyu ZhuYing WangZhihui HuangHonglin TengThe M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress–related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia–derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.https://journals.lww.com/10.4103/NRR.NRR-D-23-01256cgas/stingfunctional recoverymicroglianeuroinflammationneuroprotectionnuclear factor-κbpolarizationspinal cord injurytryptanthrin |
| spellingShingle | Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury Neural Regeneration Research cgas/sting functional recovery microglia neuroinflammation neuroprotection nuclear factor-κb polarization spinal cord injury tryptanthrin |
| title | Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury |
| title_full | Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury |
| title_fullStr | Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury |
| title_full_unstemmed | Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury |
| title_short | Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury |
| title_sort | pharmacological targeting cgas sting nf κb axis by tryptanthrin induces microglia polarization toward m2 phenotype and promotes functional recovery in a mouse model of spinal cord injury |
| topic | cgas/sting functional recovery microglia neuroinflammation neuroprotection nuclear factor-κb polarization spinal cord injury tryptanthrin |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-23-01256 |
| work_keys_str_mv | AT ziweifan pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT mengxianjia pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT jianzhou pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT zhoulezhu pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT yuminwu pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT xiaowulin pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT yimingqian pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT jiashulian pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT xinhua pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT jianhongdong pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT zheyufang pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT yuqingliu pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT sibingchen pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT xiuminxue pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT juanqingyue pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT minyuzhu pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT yingwang pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT zhihuihuang pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury AT honglinteng pharmacologicaltargetingcgasstingnfkbaxisbytryptanthrininducesmicrogliapolarizationtowardm2phenotypeandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury |