Bone marrow mesenchymal stem cell-derived exosomal miR-193b-5p reduces pyroptosis after ischemic stroke by targeting AIM2.
J Stroke Cerebrovasc Dis
; 32(8): 107235, 2023 Aug.
Article
en En
| MEDLINE
| ID: mdl-37393689
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
In the luciferase assay, miR-193b-5p showed direct binding to the 3'-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-1ß/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.CONCLUSION:
BMSC-Exos attenuate the cerebral I/R injury in vivo and in vitro by inhibiting AIM2 pathway-mediated pyroptosis through miR-193b-5p delivery.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Células Madre Mesenquimatosas
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Accidente Cerebrovascular Isquémico
/
Melanoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Stroke Cerebrovasc Dis
Asunto de la revista:
ANGIOLOGIA
/
CEREBRO
Año:
2023
Tipo del documento:
Article