The International journal of neuroscience · 2024
Exosomes derived from umbilical cord mesenchymal stem cells ameliorate ischemic brain injury in mice by regulating AAK1 via miR-664a-5p.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shen Baoxi, Liu Ning, Dai Yiwu
Аннотация
OBJECTIVE: To identify the molecular targets of mesenchymal stem cell (MSC)-derived exosomes in treating cerebral ischemia and elucidate their therapeutic mechanisms.
METHODS: We utilized a mouse model of middle cerebral artery occlusion and treated mice with umbilical cord mesenchymal stem cells derived exosomes. Proteomic analysis identified AAK1(AP2 associated kinase 1) as a key target protein. Functional studies confirmed that AAK1 modulates the NF-κB signaling pathway in ischemic stroke. MicroRNA profiling, bioinformatic prediction and cell experiments identified miR-664a-5p as the specific microRNA regulating AAK1 expression. Finally, we validated the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes using engineered miR-664a-5p-deficient exosomes.
RESULTS: Our findings demonstrate that umbilical cord mesenchymal stem cells-derived exosomes exert neuroprotective effects in ischemic stroke by modulating the AAK1/NF-κB axis via miR-664a-5p.
CONCLUSION: This study provides novel insights into the therapeutic mechanism of mesenchymal stem cell-derived exosomes in ischemic stroke, highlighting their potential for developing exosome-based therapies.
METHODS: We utilized a mouse model of middle cerebral artery occlusion and treated mice with umbilical cord mesenchymal stem cells derived exosomes. Proteomic analysis identified AAK1(AP2 associated kinase 1) as a key target protein. Functional studies confirmed that AAK1 modulates the NF-κB signaling pathway in ischemic stroke. MicroRNA profiling, bioinformatic prediction and cell experiments identified miR-664a-5p as the specific microRNA regulating AAK1 expression. Finally, we validated the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes using engineered miR-664a-5p-deficient exosomes.
RESULTS: Our findings demonstrate that umbilical cord mesenchymal stem cells-derived exosomes exert neuroprotective effects in ischemic stroke by modulating the AAK1/NF-κB axis via miR-664a-5p.
CONCLUSION: This study provides novel insights into the therapeutic mechanism of mesenchymal stem cell-derived exosomes in ischemic stroke, highlighting their potential for developing exosome-based therapies.