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首页> 外文期刊>Cell death & disease. >MiR-27b regulates podocyte survival through targeting adenosine receptor 2B in podocytes from non-human primate
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MiR-27b regulates podocyte survival through targeting adenosine receptor 2B in podocytes from non-human primate

机译：MiR-27b通过靶向非人类灵长类动物足细胞中的腺苷受体2B来调节足细胞存活

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MicroRNAs are a group of small non-coding RNAs that play key roles in almost every aspect of mammalian cell. In kidney, microRNAs are required for maintaining normal function of renal cells, disruption of which contributes to pathogenesis of renal diseases. In this study, we investigated the potential role of miRNAs as key regulators of podocyte survival by using a primary cell culture model from non-human primates (NHPs). Through microRNA profile comparison in glomeruli from mouse, rat and NHP, miR-27b was found to be among a list of glomeruli-enriched miRNA conserved across species. In NHP primary podocyte culture, significant downregulation of miR-27b was observed during treatment of puromycin aminonucleoside (PAN), a classic nephrotoxin. Overexpression of miR-27b enhanced PAN-induced apoptosis and cytoskeleton destruction in podocytes while its inhibition had a protective effect. Target identification analysis identified Adora2b as a potential direct target of miR-27b. Ectopic expression of miR-27b suppressed both Adora2b mRNA and protein expression, whereas inhibition of miR-27b increased the transcript and protein expression levels of Adora2B. Dual luciferase assay further confirmed Adora2b as a direct target of miR-27b. Furthermore, knockdown of Adora2b by siRNAs enhanced PAN-induced apoptosis, similar to the phenotypes we had observed with miR-27b overexpression. In addition, stimulating the adenosine signaling by an Adora2b agonist, NECA, improved podocyte survival upon PAN treatment. Taken together, our data identified a novel role of miR-27b-adora2b axis in primary podocyte survival upon injury and suggested a critical role of adenosine signaling pathway in podocyte protection.
机译：MicroRNA是一组小的非编码RNA，它们在哺乳动物细胞的几乎每个方面都起着关键作用。在肾脏中，microRNA是维持肾细胞正常功能所必需的，肾细胞的破坏有助于肾脏疾病的发病。在这项研究中，我们通过使用来自非人类灵长类动物（NHP）的原代细胞培养模型，研究了miRNA作为足细胞存活关键调节剂的潜在作用。通过比较小鼠，大鼠和NHP肾小球中的microRNA谱，发现miR-27b属于物种间保守的富含肾小球的miRNA列表。在NHP原代足细胞培养中，在经典的肾毒素嘌呤霉素氨基核苷（PAN）治疗期间观察到miR-27b的显着下调。 miR-27b的过表达增强了PAN诱导的足细胞凋亡和细胞骨架破坏，而其抑制则具有保护作用。靶标识别分析确定Adora2b是miR-27b的潜在直接靶标。 miR-27b的异位表达抑制了Adora2b mRNA和蛋白表达，而抑制miR-27b则增加了Adora2B的转录本和蛋白表达水平。双重荧光素酶测定法进一步证实Adora2b是miR-27b的直接靶标。此外，siRNA抑制Adora2b增强了PAN诱导的细胞凋亡，类似于我们在miR-27b过表达中观察到的表型。此外，通过Adora2b激动剂NECA刺激腺苷信号传导，可改善PAN治疗后足细胞的存活率。综上所述，我们的数据确定了miR-27b-adora2b轴在损伤后原代足细胞存活中的新作用，并暗示了腺苷信号通路在足细胞保护中的关键作用。

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