Experimental neurology · 2022
Downregulation of miR-26b attenuates early brain injury induced by subarachnoid hemorrhage via mediating the KLF4/STAT3/HMGB1 axis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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.
Huang Zewei, Liu Jialin, Xu Jiongfu, Dai Limeng, Wang Hao
Аннотация
BACKGROUND: Early brain injury (EBI) refers to early-onset secondary complications that occur after subarachnoid hemorrhage (SAH), and associated with high rate of disability and mortality. Recent investigations have indicated microRNA-26b (miR-26b) as a biomarker in the progression of SAH. Accordingly, the present study was designed to elucidate the role of miR-26b in influencing EBI following SAH and the downstream mechanisms.
METHODS: Firstly, SAH rat models and neuron injury models were developed to assess the effect of miR-26b on EBI-like symptoms and subsequent inflammation. Dual-luciferase reporter gene assay was further implemented to evaluate the binding of miR-26b to its putative target gene STAT3. Loss-of-function and rescue experiments were performed to assess the functionality of miR-26b-mediated STAT3 in both models.
RESULTS: miR-26b was found to target KLF4 and negative-modulate its expression, whereby aggravating EBI and inflammatory response in SAH rat models and stimulating hemoglobin-induced apoptosis in astrocytes. On the other hand, silencing of miR-26b reversed these changes in SAH rat models and hemoglobin (Hb)-induced astrocytes. miR-26b could further activate STAT3 via down-regulation of KLF4. Furthermore, KLF4 knockdown up-regulated HMGB1 to aggravate EBI following SAH.
CONCLUSIONS: Collectively, our findings highlighted the ameliorative effect of miR-26b inhibition on EBI in SAH and the possible mechanism associated with the KLF4/STAT3/HMGB1 axis.
METHODS: Firstly, SAH rat models and neuron injury models were developed to assess the effect of miR-26b on EBI-like symptoms and subsequent inflammation. Dual-luciferase reporter gene assay was further implemented to evaluate the binding of miR-26b to its putative target gene STAT3. Loss-of-function and rescue experiments were performed to assess the functionality of miR-26b-mediated STAT3 in both models.
RESULTS: miR-26b was found to target KLF4 and negative-modulate its expression, whereby aggravating EBI and inflammatory response in SAH rat models and stimulating hemoglobin-induced apoptosis in astrocytes. On the other hand, silencing of miR-26b reversed these changes in SAH rat models and hemoglobin (Hb)-induced astrocytes. miR-26b could further activate STAT3 via down-regulation of KLF4. Furthermore, KLF4 knockdown up-regulated HMGB1 to aggravate EBI following SAH.
CONCLUSIONS: Collectively, our findings highlighted the ameliorative effect of miR-26b inhibition on EBI in SAH and the possible mechanism associated with the KLF4/STAT3/HMGB1 axis.