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MiR-382-5p suppresses M1 macrophage polarization and inflammatory response in response to bronchopulmonary dysplasia through targeting CDK8: Involving inhibition of STAT1 pathway

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机构: [1]Department of Pediatrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China [2]Department of Pediatrics, Baoding First Central Hospital, Baoding, China [3]Department of Pediatrics, Hebei General Hospital, Shijiazhuang, China [4]Department of Laboratory Medicine, Baoding No. 1 Hospital of TCM, Baoding, China
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关键词: bronchopulmonary dysplasia CDK8 M1 macrophage miR-382-5p STAT1

摘要:
Bronchopulmonary dysplasia (BPD) is an inflammation-related respiratory disorder in infants. MiR-382-5p has displayed low expression in developing lungs with BPD, while the effect of miR-382-5p on BPD remains elusive. Here, a hyperoxia (85% oxygen)-induced BPD model in neonatal mice was established. On postnatal days 10 and 15, hyperoxia reduced miR-382-5p expression in lungs of mice. Besides, CDK8, CD68 and CD86 levels were elevated on day 15 after birth, implying the involvement of CDK8 in M1 macrophage polarization. In addition, in vitro injury in RAW264.7 macrophages was induced by IFN-gamma and LPS stimulation. Lentivirus-encoding miR-382-5p decreased CDK8 expression, alleviated the production of inflammatory cytokines TNF-alpha, IL-1 beta and IL-6, and restricted the levels of CD40 and CD86 in response to IFN-gamma and LPS. Moreover, miR-382-5p inhibited the phosphorylation of STAT1. Luciferase reporter assay verified that miR-382-5p might target the 3 ' UTR of CDK8. Rescue assays revealed that CDK8 reversed the mitigating roles of miR-382-5p in inflammatory response and M1 macrophage polarization, as reflected by increased IL-6 and CD40 levels. Taken together, these findings indicate that miR-382-5p may suppress M1 macrophage activation and inflammatory response via inhibiting CDK8, thereby regulating the development of BPD, which is possibly mediated by STAT1 signaling.

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出版当年[2021]版:
大类 | 4 区 生物
小类 | 4 区 细胞生物学 4 区 遗传学
最新[2025]版:
大类 | 4 区 生物学
小类 | 4 区 细胞生物学 4 区 遗传学
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出版当年[2021]版:
Q3 GENETICS & HEREDITY Q4 CELL BIOLOGY
最新[2024]版:
Q4 CELL BIOLOGY Q4 GENETICS & HEREDITY

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第一作者机构: [1]Department of Pediatrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China [2]Department of Pediatrics, Baoding First Central Hospital, Baoding, China
通讯作者:
通讯机构: [1]Department of Pediatrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China [*1]Department of Pediatrics, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang, Hebei 050011, China.
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