Resveratrol Upregulates miR-124-3p Expression to Target DAPK1, Regulating the NLRP3/Caspase-1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury
机构:[1]Kunming Med Univ, Affiliated Hosp 1, Dept Orthoped, Yunnan, Peoples R China昆明医科大学附属第一医院[2]Xi Chang Peoples Hosp, Dept Crit Care Med, Sichuan, Peoples R China
Currently, an effective treatment for spinal cord injury (SCI) is not available. Due to the irreversible primary injury associated with SCI, the prevention and treatment of secondary injury are very important. In the secondary injury stage, pyroptosis exacerbates the deterioration of the spinal cord injury, and inhibiting pyroptosis is beneficial for recovery from SCI. The aim of this study was to clarify the role of resveratrol (RES) and the antipyroptotic mechanisms of RES and miR-124-3p in SCI to lay a theoretical foundation for the clinical treatment of SCI and provide new therapeutic approaches. Using cell staining and related molecular protein detection techniques to assess DAPK1, the effects of miR-124-3p and RES on pyroptosis were investigated, and the effects of RES on injured spinal cord repair in rats were evaluated using tissue staining and related functional recovery experiments. In vitro, DAPK1 interacts with NLRP3, exerting a pyroptotic effect through the NLRP3/Caspase-1/GSDMD pathway and DAPK1 knockdown inhibits pyroptosis. miR-124-3P negatively regulates the level of DAPK1 and reduced cell pyroptosis. RES increased miR-124-3p expression and reduces DAPK1 expression, affecting the NLRP3/Caspase-1/GSDMD pathway and inhibiting pyroptosis. In vivo, RES reduces GSDMD-N levels in rats with SCI, promotes functional recovery, and thus promotes recovery from SCI. Therefore, we concluded that RES increases the level of miR-124-3p, which targets DAPK1, regulates the NLRP3/Caspase-1/GSDMD pathway, inhibits pyroptosis and alleviates SCI.
基金:
Yunnan Fundamental Research Projects. National Natural Science Foundation of China. Priority Union
Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University. The Major Science and Technology Project of
Yunnan Provincial Department of Science and Technology, Yunnan Provincial Orthopedic and Sports Rehabilitation Clinical Medicine Research Center.
First-Class Discipline Team of Kunming Medical University. 535 Talent Project of First Affiliated Hospital of Kunming Medical University. Yunnan
Revitalization Talent Support Program. Yunnan Health Training Project of High Level Talent.
第一作者机构:[1]Kunming Med Univ, Affiliated Hosp 1, Dept Orthoped, Yunnan, Peoples R China
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通讯作者:
推荐引用方式(GB/T 7714):
Li Daohui,Dai Yongwen,Li Zhengtao,et al.Resveratrol Upregulates miR-124-3p Expression to Target DAPK1, Regulating the NLRP3/Caspase-1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury[J].JOURNAL OF CELLULAR AND MOLECULAR MEDICINE.2025,29(2):doi:10.1111/jcmm.70338.
APA:
Li, Daohui,Dai, Yongwen,Li, Zhengtao,Bi, Hangchuan,Li, Haotian...&Chen, Lingqiang.(2025).Resveratrol Upregulates miR-124-3p Expression to Target DAPK1, Regulating the NLRP3/Caspase-1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,29,(2)
MLA:
Li, Daohui,et al."Resveratrol Upregulates miR-124-3p Expression to Target DAPK1, Regulating the NLRP3/Caspase-1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 29..2(2025)