Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels
Abstract Background Peripheral nerve injury (PNI) is commonly observed in clinical practice, yet the underlying mechanisms remain unclear. This study investigated the correlation between the expression of a Ras-related protein Rab32 and pyroptosis in rats following PNI, and potential mechanisms have...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-04999-x |
| _version_ | 1797273455145517056 |
|---|---|
| author | Jiayi Wang Pin Chen Guanjie Han Yongjie Zhou Xingdong Xiang Mengxuan Bian Lei Huang Xiang Wang Binfeng He Shunyi Lu |
| author_facet | Jiayi Wang Pin Chen Guanjie Han Yongjie Zhou Xingdong Xiang Mengxuan Bian Lei Huang Xiang Wang Binfeng He Shunyi Lu |
| author_sort | Jiayi Wang |
| collection | DOAJ |
| description | Abstract Background Peripheral nerve injury (PNI) is commonly observed in clinical practice, yet the underlying mechanisms remain unclear. This study investigated the correlation between the expression of a Ras-related protein Rab32 and pyroptosis in rats following PNI, and potential mechanisms have been explored by which Rab32 may influence Schwann cells pyroptosis and ultimately peripheral nerve regeneration (PNR) through the regulation of Reactive oxygen species (ROS) levels. Methods The authors investigated the induction of Schwann cell pyroptosis and the elevated expression of Rab32 in a rat model of PNI. In vitro experiments revealed an upregulation of Rab32 during Schwann cell pyroptosis. Furthermore, the effect of Rab32 on the level of ROS in mitochondria in pyroptosis model has also been studied. Finally, the effects of knocking down the Rab32 gene on PNR were assessed, morphology, sensory and motor functions of sciatic nerves, electrophysiology and immunohistochemical analysis were conducted to assess the therapeutic efficacy. Results Silencing Rab32 attenuated PNI-induced Schwann cell pyroptosis and promoted peripheral nerve regeneration. Furthermore, our findings demonstrated that Rab32 induces significant oxidative stress by damaging the mitochondria of Schwann cells in the pyroptosis model in vitro. Conclusion Rab32 exacerbated Schwann cell pyroptosis in PNI model, leading to delayed peripheral nerve regeneration. Rab32 can be a potential target for future therapeutic strategy in the treatment of peripheral nerve injuries. |
| first_indexed | 2024-03-07T14:43:30Z |
| format | Article |
| id | doaj.art-3c6532b4b58b4d2daa9236526c3a4d78 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T14:43:30Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-3c6532b4b58b4d2daa9236526c3a4d782024-03-05T20:07:24ZengBMCJournal of Translational Medicine1479-58762024-02-0122111710.1186/s12967-024-04999-xRab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levelsJiayi Wang0Pin Chen1Guanjie Han2Yongjie Zhou3Xingdong Xiang4Mengxuan Bian5Lei Huang6Xiang Wang7Binfeng He8Shunyi Lu9Department of Orthopedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Neurosurgery, Zhongshan Hospital, Fudan UniversityDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Interventional Radiology, Zhongshan Hospital, Fudan UniversityDepartment of Rehabilitation, Zhongshan Hospital, Fudan UniversityDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan UniversityAbstract Background Peripheral nerve injury (PNI) is commonly observed in clinical practice, yet the underlying mechanisms remain unclear. This study investigated the correlation between the expression of a Ras-related protein Rab32 and pyroptosis in rats following PNI, and potential mechanisms have been explored by which Rab32 may influence Schwann cells pyroptosis and ultimately peripheral nerve regeneration (PNR) through the regulation of Reactive oxygen species (ROS) levels. Methods The authors investigated the induction of Schwann cell pyroptosis and the elevated expression of Rab32 in a rat model of PNI. In vitro experiments revealed an upregulation of Rab32 during Schwann cell pyroptosis. Furthermore, the effect of Rab32 on the level of ROS in mitochondria in pyroptosis model has also been studied. Finally, the effects of knocking down the Rab32 gene on PNR were assessed, morphology, sensory and motor functions of sciatic nerves, electrophysiology and immunohistochemical analysis were conducted to assess the therapeutic efficacy. Results Silencing Rab32 attenuated PNI-induced Schwann cell pyroptosis and promoted peripheral nerve regeneration. Furthermore, our findings demonstrated that Rab32 induces significant oxidative stress by damaging the mitochondria of Schwann cells in the pyroptosis model in vitro. Conclusion Rab32 exacerbated Schwann cell pyroptosis in PNI model, leading to delayed peripheral nerve regeneration. Rab32 can be a potential target for future therapeutic strategy in the treatment of peripheral nerve injuries.https://doi.org/10.1186/s12967-024-04999-xPeripheral nerve regenerationPyroptosisSchwann cellsRab32 |
| spellingShingle | Jiayi Wang Pin Chen Guanjie Han Yongjie Zhou Xingdong Xiang Mengxuan Bian Lei Huang Xiang Wang Binfeng He Shunyi Lu Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels Journal of Translational Medicine Peripheral nerve regeneration Pyroptosis Schwann cells Rab32 |
| title | Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels |
| title_full | Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels |
| title_fullStr | Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels |
| title_full_unstemmed | Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels |
| title_short | Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels |
| title_sort | rab32 facilitates schwann cell pyroptosis in rats following peripheral nerve injury by elevating ros levels |
| topic | Peripheral nerve regeneration Pyroptosis Schwann cells Rab32 |
| url | https://doi.org/10.1186/s12967-024-04999-x |
| work_keys_str_mv | AT jiayiwang rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT pinchen rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT guanjiehan rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT yongjiezhou rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT xingdongxiang rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT mengxuanbian rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT leihuang rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT xiangwang rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT binfenghe rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels AT shunyilu rab32facilitatesschwanncellpyroptosisinratsfollowingperipheralnerveinjurybyelevatingroslevels |