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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1454116
Astrocyte-derived exosomal miR-378a-5p mitigates cerebral ischemic neuroinflammation by modulating NLRP3-mediated pyroptosis
Provisionally accepted
Ruiting Sun
1*
Wenxin Liao
1
Ting Lang
1*
Keyi Qin
1*
Keyan Jiao
1
Le Shao
1,2*
Changqing Deng
1*
Yan She
1*- 1 Hunan University of Chinese Medicine, Changsha, China
- 2 The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
Objective: This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia.Methods: Astrocyte-derived exosomes were studied for treating cerebral ischemia in both in vitro and in vivo models. The effects of astrocyte-derived exosomes on neuroinflammation were investigated by analyzing exosome uptake, nerve damage, and pyroptosis protein expression. High throughput sequencing was used to identify astrocyte-derived exosomal miRNAs linked to pyroptosis, followed by validation via qRT-PCR. The relationship between these miRNAs and NLRP3 was studied using a dual luciferase reporter assay. This study used miR-378a-5p overexpression and knockdown to manipulate OGD injury in nerve cells. The impact of astrocyte-derived exosomal miR-378a-5p on the regulation of cerebral ischemic neuroinflammation was assessed through analysis of nerve injury and pyroptosis-related protein expression.Our findings demonstrated that astrocyte-derived exosomes were internalized by neurons both in vitro and in vivo. Additionally, Astrocyte-derived exosomes displayed a neuroprotective effect against OGD-induced neuronal injury and brain injury in the ischemic cortical region of middle cerebral artery occlusion (MCAO) rats while also reducing pyroptosis. Further investigations revealed the involvement of astrocyte-derived exosomal miR-378a-5p in regulating pyroptosis by inhibiting NLRP3. The overexpression of miR-378a-5p mitigated neuronal damage, whereas the knockdown of miR-378a-5p increased NLRP3 expression and exacerbated pyroptosis, thus reversing this neuroprotective effect.Astrocyte-derived exosomal miR-378a-5p has a neuroprotective effect on cerebral ischemia by suppressing neuroinflammation associated with NLRP3-mediated pyroptosis.Further research is required to comprehensively elucidate the signaling pathways by which astrocyte-derived exosomal miR-378a-5p modulates neuronal pyroptosis.
Keywords: Astrocyte-derived exosomes, pyroptosis, Inflammation, cerebral ischemia, NLRP3, miR-378a-5p
Received: 24 Jun 2024; Accepted: 22 Jul 2024.
Copyright: © 2024 Sun, Liao, Lang, Qin, Jiao, Shao, Deng and She. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ruiting Sun, Hunan University of Chinese Medicine, Changsha, China
Ting Lang, Hunan University of Chinese Medicine, Changsha, China
Keyi Qin, Hunan University of Chinese Medicine, Changsha, China
Le Shao, Hunan University of Chinese Medicine, Changsha, China
Changqing Deng, Hunan University of Chinese Medicine, Changsha, China
Yan She, Hunan University of Chinese Medicine, Changsha, China
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