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Research Article

BNIP3介导的自噬诱导的炎症反应和抑制缺氧条件下培养的视网膜色素上皮细胞VEGF表达。

卷 19, 期 6, 2019

页: [395 - 404] 页: 10

弟呕挨: 10.2174/1566524019666190509105502

价格: $65

摘要

背景：Bcl-2 /腺病毒E1B-19kDa相互作用蛋白（BNIP3）是缺氧诱导因子-1α（HIF-1α）的重要靶点，据报道在低氧条件下过表达。我们之前的研究证明了BNIP3介导的自噬对视网膜脱离的保护作用。本研究探讨了BNIP3介导的自噬在缺氧条件下视网膜色素上皮细胞（RPE）中的作用，并观察了缺氧RPE细胞中BNIP3，血管内皮生长因子（VEGF）与炎症反应的关系。 方法：通过小干扰RNA（siRNA）技术在人RPE细胞系ARPE-19细胞中进行BNIP3敲低视网膜色素上皮细胞。然后使用氯化钴（II）（CoCl 2）对对照和BNIP3敲低的ARPE-19细胞进行低氧攻击。使用定量聚合酶链反应（qPCR）检查RPE细胞中自噬相关基因，VEGF和炎性因子（IL-18，IL-8，MMP-2，MMP-9，NLRP3，TNF-α）的表达。 HIF-1α，BNIP3，自噬的制造蛋白（ATG5，LC3，p62，Beclin-1）和mTORC1途径的组分蛋白（p-p70S6K，p70S6K，mTOR，p-mTOR）的蛋白水平进行了分析。蛋白质印迹。通过免疫荧光检测BNIP3亚细胞定位。用细胞计数试剂盒-8测量细胞活力。通过TUNEL染色和胱天蛋白酶-3活性测定检查细胞凋亡。 结果：缺氧条件下，ARPE-19细胞中BNIP3，HIF-1α和自噬标记基因的表达水平上调。重要的是，缺氧诱导的自噬是由mTORC1途径介导的，并且在BNIP3敲低后被阻断。此外，缺氧降低了细胞活力，mTORC1抑制剂缓解了细胞活力。此外，自噬保护ARPE-19细胞免受CoCl2诱导的细胞凋亡。此外，抑制自噬上调VEGF和IL-18的表达，并下调低氧ARPE-19细胞中其他炎症因子的表达。 结论：缺氧条件下BNIP3介导的自噬参与调节炎症反应和血管内皮生长因子的表达，从而影响RPE细胞的细胞活力。

关键词: BNIP3，缺氧，RPEs，自噬，VEGF，炎症。

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