RNA-Binding Proteins HuB, HuC, and HuD are Distinctly Regulated in Dorsal Root Ganglia Neurons from STZ-Sensitive Compared to STZ-Resistant Diabetic Mice
RNA-Binding Proteins HuB, HuC, and HuD are Distinctly Regulated in Dorsal Root Ganglia Neurons from STZ-Sensitive Compared to STZ-Resistant Diabetic Mice
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DOI：
10.3390/ijms20081965
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发表时间：
2019-04-02
影响因子：
5.6
通讯作者：
Radu, Beatrice Mihaela
中科院分区：
文献类型：
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作者：
Mustaciosu, Cosmin Catalin;Banciu, Adela;Radu, Beatrice Mihaela
神经元特异性的Elav-like Hu RNA结合蛋白被描述为通过确保编码各种蛋白质的RNA的转录后控制在神经元分化和可塑性中发挥重要作用。尽管Elav-like Hu蛋白在糖尿病或神经病变中有报道，但由于糖尿病条件，对背根神经节（DRG）感觉神经元中神经元特异性Elav-like Hu RNA结合蛋白的调节知之甚少。本研究的目的是分析糖尿病患者DRG感觉神经元中HuB、HuC和HuD的基因和蛋白表达。通过单次腹腔注射链脲佐菌素（STZ，150 mg/kg）在CD-1成年雄性小鼠中诱导糖尿病状况，并在诱导后8周（晚期糖尿病）定量Elav样蛋白表达。基于STZ值，我们鉴定了对STZ的两种类型的反应，并且将小鼠分类为STZ抗性（糖尿病抗性，STZ < 260 mg/dL）和STZ敏感性（糖尿病，STZ> 260 mg/dL）。体重测量表明，在STZ诱导糖尿病后8周，与糖尿病小鼠和糖尿病抗性小鼠相比，对照小鼠的体重增加更高。此外，8周后，在热板试验中，糖尿病小鼠（19.52 +/- 3.52 s）具有比糖尿病抗性小鼠（11.36 +/- 1.92 s）和对照小鼠（11.03 +/- 1.97 s）更长的缩爪延迟，这与由于糖尿病状况引起的温暖痛觉减退的发生相关。进一步，我们证实了糖尿病小鼠DRG神经元中Elav样基因表达的减少（Elavl 2，0.68 +/-0.05倍; Elavl 3，0.65 +/-0.01倍; Elavl 4，0.53 +/-0.07倍）和糖尿病抗性小鼠07倍; Elavl 3，0.32 +/-0.09倍）。有趣的是，Elav样基因在糖尿病抗性小鼠中的下调比在糖尿病小鼠中更明显，尽管仅在糖尿病小鼠中证明了痛觉减退。Elav样基因表达的变化并不总是与Hu蛋白表达的变化相关。详细地说，与对照小鼠相比，糖尿病小鼠中HuB上调，HuD下调，而糖尿病抗性小鼠中HuB、HuC和HuD下调。为了恢复，我们证明了由糖尿病诱导的DRG感觉神经元中HuD下调和HuB上调，这可能与参与由晚期糖尿病神经病变引起的热痛觉减退状况的调节的RNA的转录后控制改变相关。
The neuron-specific Elav-like Hu RNA-binding proteins were described to play an important role in neuronal differentiation and plasticity by ensuring the post-transcriptional control of RNAs encoding for various proteins. Although Elav-like Hu proteins alterations were reported in diabetes or neuropathy, little is known about the regulation of neuron-specific Elav-like Hu RNA-binding proteins in sensory neurons of dorsal root ganglia (DRG) due to the diabetic condition. The goal of our study was to analyze the gene and protein expression of HuB, HuC, and HuD in DRG sensory neurons in diabetes. The diabetic condition was induced in CD-1 adult male mice with single-intraperitoneal injection of streptozotocin (STZ, 150 mg/kg), and 8-weeks (advanced diabetes) after induction was quantified the Elav-like proteins expression. Based on the glycemia values, we identified two types of responses to STZ, and mice were classified in STZ-resistant (diabetic resistant, glycemia < 260 mg/dL) and STZ-sensitive (diabetic, glycemia > 260 mg/dL). Body weight measurements indicated that 8-weeks after STZ-induction of diabetes, control mice have a higher increase in body weight compared to the diabetic and diabetic resistant mice. Moreover, after 8-weeks, diabetic mice (19.52 +/- 3.52 s) have longer paw withdrawal latencies in the hot-plate test than diabetic resistant (11.36 +/- 1.92 s) and control (11.03 +/- 1.97 s) mice, that correlates with the installation of warm hypoalgesia due to the diabetic condition. Further on, we evidenced the decrease of Elav-like gene expression in DRG neurons of diabetic mice (Elavl2, 0.68 +/- 0.05 fold; Elavl3, 0.65 +/- 0.01 fold; Elavl4, 0.53 +/- 0.07 fold) and diabetic resistant mice (Ealvl2, 0.56 +/- 0.07 fold; Elavl3, 0.32 +/- 0.09 fold) compared to control mice. Interestingly, Elav-like genes have a more accentuated downregulation in diabetic resistant than in diabetic mice, although hypoalgesia was evidenced only in diabetic mice. The Elav-like gene expression changes do not always correlate with the Hu protein expression changes. To detail, HuB is upregulated and HuD is downregulated in diabetic mice, while HuB, HuC, and HuD are downregulated in diabetic resistant mice compared to control mice. To resume, we demonstrated HuD downregulation and HuB upregulation in DRG sensory neurons induced by diabetes, which might be correlated with altered post-transcriptional control of RNAs involved in the regulation of thermal hypoalgesia condition caused by the advanced diabetic neuropathy.