Bone marrow mesenchymal stem cell-derived exosomal miR-193b-5p reduces pyroptosis after ischemic stroke by targeting AIM2

•AIM2 is a target gene of miR-193b-5p.•Over expression of miR-193b-5p reduced pyroptosis and increased cell activity in OGD/R PC12 cells by AIM2 pathway.•miR-193b-5p-overexpressing exosomes had a greater effect in inhibiting AIM2 pathway-mediated pyroptosis in both in vivo and in vitro assays.•BMSC-...

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Published in:Journal of stroke and cerebrovascular diseases 2023-08, Vol.32 (8), p.107235-107235, Article 107235
Main Authors: Wang, Yingju, Chen, Hongping, Fan, Xuehui, Xu, Chen, Li, Meng, Sun, Hongxue, Song, Jihe, Jia, Feihong, Wei, Wan, Jiang, Fangchao, Li, Guozhong, Zhong, Di
Format: Article
Language:English
Subjects:
AIM2
BMSCs
cerebral ischemia-reperfusion injury
exosomes
miR-193b-5p
pyroptosis
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Summary:•AIM2 is a target gene of miR-193b-5p.•Over expression of miR-193b-5p reduced pyroptosis and increased cell activity in OGD/R PC12 cells by AIM2 pathway.•miR-193b-5p-overexpressing exosomes had a greater effect in inhibiting AIM2 pathway-mediated pyroptosis in both in vivo and in vitro assays.•BMSC-Exos attenuate cerebral I/R injury by inhibiting AIM2 pathway-mediated pyroptosis through miR-193b-5p delivery. Ischemic stroke represents a major factor causing global morbidity and death. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (Exos) have important effects on treating ischemic stroke. Here, we investigated the therapeutic mechanism by which BMSC-derived exosomal miR-193b-5p affects ischemic stroke. luciferase assay was performed to evaluate the regulatory relationship of miR-193b-5p with absent in melanoma 2 (AIM2). Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed for the in vitro assay, while a middle cerebral artery occlusion (MCAO) model was developed for the in vivo assay. After exosome therapy, lactate dehydrogenase and MTT assays were conducted to detect cytotoxicity and cell viability, while PCR, ELISA, western blotting assay, and immunofluorescence staining were performed to detect changes in the levels of pyroptosis-related molecules. TTC staining and TUNEL assays were performed to assess cerebral ischemia/reperfusion (I/R) injury. In the luciferase assay, miR-193b-5p showed direct binding to the 3ʹ-untranslated region of AIM2. In both in vivo and in vitro assays, the injected exosomes could access the sites of ischemic injury and could be internalized. In the in vitro assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on increasing cell viability and attenuating cytotoxicity; AIM2, GSDMD-N, and cleaved caspase-1 levels; and IL-1β/IL-18 generation. In the in vivo assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on decreasing the levels of these pyroptosis-related molecules and infarct volume. BMSC-Exos attenuate the cerebral I/R injury in vivo and in vitro by inhibiting AIM2 pathway-mediated pyroptosis through miR-193b-5p delivery.
ISSN:1052-3057
1532-8511
DOI:10.1016/j.jstrokecerebrovasdis.2023.107235