miR-19a/b-3p promotes inflammation during cerebral ischemia/reperfusion injury via SIRT1/FoxO3/SPHK1 pathway.
miR-19a/b-3p promotes inflammation during cerebral ischemia/reperfusion injury via SIRT1/FoxO3/SPHK1 pathway.
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miR-19a/b-3p通过SIRT1/FoxO3/SPHK1通路促进脑缺血/再灌注损伤过程中的炎症
DOI：
10.1186/s12974-021-02172-5
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发表时间：
2021-05-29
影响因子：
9.3
通讯作者：
Wu BY
中科院分区：
文献类型：
--
作者：
Zhou F;Wang YK;Zhang CG;Wu BY
中风影响3-4%的成年人，每年造成许多人死亡。在最小的再灌注损伤下恢复血流至关重要。然而，再灌注诱导的损伤，特别是炎症的机制还不清楚。本研究探讨miR-19 a/B-3 p/SIRT 1/FoxO 3/SPHK 1轴在缺血/再灌注（I/R）中的作用。采用大鼠大脑中动脉闭塞（MCAO）再灌注模型作为I/R的体内模型。采用体外培养的神经元细胞进行OGD/R（氧糖剥夺/再灌注）作为I/R的体外模型。MTT法检测细胞活力，TUNEL法检测细胞凋亡。H&E染色用于检查细胞形态。进行qRT-PCR和蛋白质印迹以确定miR-19 a/B-3 p、SIRT 1、FoxO 3、SPHK 1、NF-κB p65和细胞因子如TNF-α、IL-6和IL-1β的水平。通过EMSA和ChIP验证FoxO 3与SPHK 1启动子的相互作用。采用双荧光素酶法和RIP验证miR-19 a/B-3 p与SIRT 1 mRNA的结合。在MCAO/再灌注后的脑组织或OGD/R后的细胞中，miR-19 a/B-3 p、FoxO 3、SPHK 1、NF-κB p65和细胞因子升高，而SIRT 1降低。SPHK 1或FoxO 3的敲低抑制I/R诱导的炎症和细胞死亡。此外，FoxO 3的敲低逆转了SIRT 1敲低的影响。抑制miR-19 a/B-3 p可抑制炎症，这种抑制作用可被SIRT 1敲低阻断。FoxO 3结合SPHK 1启动子并激活其转录。miR-19 a/B-3 p直接靶向SIRT 1 mRNA。miR-19 a/B-3 p通过靶向SIRT 1/FoxO 3/SPHK 1轴促进I/R期间的炎症反应。
Stroke affects 3–4% of adults and kills numerous people each year. Recovering blood flow with minimal reperfusion-induced injury is crucial. However, the mechanisms underlying reperfusion-induced injury, particularly inflammation, are not well understood. Here, we investigated the function of miR-19a/b-3p/SIRT1/FoxO3/SPHK1 axis in ischemia/reperfusion (I/R). MCAO (middle cerebral artery occlusion) reperfusion rat model was used as the in vivo model of I/R. Cultured neuronal cells subjected to OGD/R (oxygen glucose deprivation/reperfusion) were used as the in vitro model of I/R. MTT assay was used to assess cell viability and TUNEL staining was used to measure cell apoptosis. H&E staining was employed to examine cell morphology. qRT-PCR and western blot were performed to determine levels of miR-19a/b-3p, SIRT1, FoxO3, SPHK1, NF-κB p65, and cytokines like TNF-α, IL-6, and IL-1β. EMSA and ChIP were performed to validate the interaction of FoxO3 with SPHK1 promoter. Dual luciferase assay and RIP were used to verify the binding of miR-19a/b-3p with SIRT1 mRNA. miR-19a/b-3p, FoxO3, SPHK1, NF-κB p65, and cytokines were elevated while SIRT1 was reduced in brain tissues following MCAO/reperfusion or in cells upon OGD/R. Knockdown of SPHK1 or FoxO3 suppressed I/R-induced inflammation and cell death. Furthermore, knockdown of FoxO3 reversed the effects of SIRT1 knockdown. Inhibition of the miR-19a/b-3p suppressed inflammation and this suppression was blocked by SIRT1 knockdown. FoxO3 bound SPHK1 promoter and activated its transcription. miR-19a/b-3p directly targeted SIRT1 mRNA. miR-19a/b-3p promotes inflammatory responses during I/R via targeting SIRT1/FoxO3/SPHK1 axis.
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辣椒素通过下调 NMDA 受体保护皮质神经元免受缺血/再灌注损伤
影响因子：
5.3
作者：
Huang M;Cheng G;Tan H;Qin R;Zou Y;Wang Y;Zhang Y
通讯作者：
Zhang Y
影响因子：
4.8
作者：
Lee, Donghoon;Goldberg, Alfred L.
通讯作者：
Goldberg, Alfred L.
影响因子：
9.3
作者：
Ding M;Lei J;Han H;Li W;Qu Y;Fu E;Fu F;Wang X
通讯作者：
Wang X
影响因子：
4.1
作者：
Kawabori M;Yenari MA
通讯作者：
Yenari MA
DOI：
10.1212/con.0000000000000416
发表时间：
2017-02-01
期刊：
Continuum (Minneapolis, Minn.)
影响因子：
--
作者：
Guzik, Amy;Bushnell, Cheryl
通讯作者：
Bushnell, Cheryl