Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats
Background. Peripheral nerve injury (PNI) is one of the most debilitating injuries, but therapies for PNI are still far from satisfactory. Pyroptosis, a recently identified form of cell death, has been demonstrated to participate in different diseases. However, the role of pyroptosis of Schwann cell...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2023/9721375 |
| _version_ | 1827088883706232832 |
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| author | Jiayi Wang Shunyi Lu Ya Yuan Lei Huang Mengxuan Bian Jieqin Yu Jiapeng Zou Libo Jiang Dehua Meng Jian Zhang |
| author_facet | Jiayi Wang Shunyi Lu Ya Yuan Lei Huang Mengxuan Bian Jieqin Yu Jiapeng Zou Libo Jiang Dehua Meng Jian Zhang |
| author_sort | Jiayi Wang |
| collection | DOAJ |
| description | Background. Peripheral nerve injury (PNI) is one of the most debilitating injuries, but therapies for PNI are still far from satisfactory. Pyroptosis, a recently identified form of cell death, has been demonstrated to participate in different diseases. However, the role of pyroptosis of Schwann cells in PNI remains unclear. Methods. We established a rat PNI model, and western blotting, transmission electron microscopy, and immunofluorescence staining were used to confirm pyroptosis of Schwann cells in PNI in vivo. In vitro, pyroptosis of Schwann cells was induced by lipopolysaccharides (LPS)+adenosine triphosphate disodium (ATP). An irreversible inhibitor of pyroptosis, acetyl (Ac)-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk), was used to attenuate Schwann cell pyroptosis. Moreover, the influence of pyroptotic Schwann cells on the function of dorsal root ganglion neurons (DRGns) was analyzed by a coculture system. Finally, the rat PNI model was intraperitoneally treated with Ac-YVAD-cmk to observe the effect of pyroptosis on nerve regeneration and motor function. Results. Schwann cell pyroptosis was notably observed in the injured sciatic nerve. LPS+ATP treatment effectively induced Schwann cell pyroptosis, which was largely attenuated by Ac-YVAD-cmk. Additionally, pyroptotic Schwann cells inhibited the function of DRGns by secreting inflammatory factors. A decrease in pyroptosis in Schwann cells promoted regeneration of the sciatic nerve and recovery of motor function in rats. Conclusion. Given the role of Schwann cell pyroptosis in PNI progression, inhibition of Schwann cell pyroptosis might be a potential therapeutic strategy for PNI in the future. |
| first_indexed | 2024-04-09T14:43:34Z |
| format | Article |
| id | doaj.art-8022514018874289954b529336283cfa |
| institution | Directory Open Access Journal |
| issn | 1466-1861 |
| language | English |
| last_indexed | 2025-03-20T05:15:42Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj.art-8022514018874289954b529336283cfa2024-10-03T05:28:04ZengHindawi LimitedMediators of Inflammation1466-18612023-01-01202310.1155/2023/9721375Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in RatsJiayi Wang0Shunyi Lu1Ya Yuan2Lei Huang3Mengxuan Bian4Jieqin Yu5Jiapeng Zou6Libo Jiang7Dehua Meng8Jian Zhang9Department of Orthopedic SurgeryDepartment of Orthopedic SurgeryDepartment of RehabilitationDepartment of Orthopedic SurgeryDepartment of Orthopedic SurgeryDepartment of Orthopedic SurgeryDepartment of Orthopedic SurgeryDepartment of Orthopedic SurgeryDepartment of Orthopedic SurgeryDepartment of Orthopedic SurgeryBackground. Peripheral nerve injury (PNI) is one of the most debilitating injuries, but therapies for PNI are still far from satisfactory. Pyroptosis, a recently identified form of cell death, has been demonstrated to participate in different diseases. However, the role of pyroptosis of Schwann cells in PNI remains unclear. Methods. We established a rat PNI model, and western blotting, transmission electron microscopy, and immunofluorescence staining were used to confirm pyroptosis of Schwann cells in PNI in vivo. In vitro, pyroptosis of Schwann cells was induced by lipopolysaccharides (LPS)+adenosine triphosphate disodium (ATP). An irreversible inhibitor of pyroptosis, acetyl (Ac)-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk), was used to attenuate Schwann cell pyroptosis. Moreover, the influence of pyroptotic Schwann cells on the function of dorsal root ganglion neurons (DRGns) was analyzed by a coculture system. Finally, the rat PNI model was intraperitoneally treated with Ac-YVAD-cmk to observe the effect of pyroptosis on nerve regeneration and motor function. Results. Schwann cell pyroptosis was notably observed in the injured sciatic nerve. LPS+ATP treatment effectively induced Schwann cell pyroptosis, which was largely attenuated by Ac-YVAD-cmk. Additionally, pyroptotic Schwann cells inhibited the function of DRGns by secreting inflammatory factors. A decrease in pyroptosis in Schwann cells promoted regeneration of the sciatic nerve and recovery of motor function in rats. Conclusion. Given the role of Schwann cell pyroptosis in PNI progression, inhibition of Schwann cell pyroptosis might be a potential therapeutic strategy for PNI in the future.http://dx.doi.org/10.1155/2023/9721375 |
| spellingShingle | Jiayi Wang Shunyi Lu Ya Yuan Lei Huang Mengxuan Bian Jieqin Yu Jiapeng Zou Libo Jiang Dehua Meng Jian Zhang Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats Mediators of Inflammation |
| title | Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats |
| title_full | Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats |
| title_fullStr | Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats |
| title_full_unstemmed | Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats |
| title_short | Inhibition of Schwann Cell Pyroptosis Promotes Nerve Regeneration in Peripheral Nerve Injury in Rats |
| title_sort | inhibition of schwann cell pyroptosis promotes nerve regeneration in peripheral nerve injury in rats |
| url | http://dx.doi.org/10.1155/2023/9721375 |
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