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CHRNA1 promotes the pathogenesis of primary focal hyperhidrosis
Molecular and Cellular Neuroscience ( IF 3.5 ) Pub Date : 2021-01-19 , DOI: 10.1016/j.mcn.2021.103598
Jian-Bo Lin 1 , Ming-Qiang Kang 2 , Li-Ping Huang 3 , Yi Zhuo 4 , Xu Li 5 , Fan-Cai Lai 4
Affiliation  

The aim of the study was to elucidate the involvement of cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in the pathogenesis of primary focal hyperhidrosis (PFH). The hyperhidrosis mouse model was constructed using pilocarpine injection. The expression levels of CHRNA1 in sweat gland tissues of PFH patients and hyperhidrosis mice were compared using Western blots and quantitative real-time PCR (qRT-PCR) analyses. Sweat secretion in hyperhidrosis mice treated with small-interfering RNA (siRNA) targeting CHRNA1 (si-CHRNA1) or non-specific siRNA were compared. Sweat secretory granules in the sweat gland cells of hyperhidrosis mice were examined using transmission electron microscopy. The serum level of acetylcholine was measured using enzyme-linked immunosorbent assay, while markers associated with PFH, including Aquaporin 5 (AQP5) and Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), were assessed using immunohistochemical assay and Western blots. Brain-derived neurotrophic factor (BDNF) and Neuregulin 1 (NRG-1) in sympathetic ganglia axons of hyperhidrosis mice were quantified using Western blots. CHRNA1 up-regulation is a characteristic of the sweat glands of PFH patients and Hyperhidrosis mice. Silencing CHRNA1 decreased sweat secretion and the number of sweat secretory granules of hyperhidrosis mice. Serum acetylcholine, as well as AQP5 and CACNA1C expression in the sweat glands, was reduced by siCHRNA1. BDNF1 and NRG-1 levels in the sympathetic ganglia axons were also attenuated by siCHRNA1 treatment. CHRNA1 up-regulation is a potential biomarker of PFH and downregulating CHRNA1 could alleviate the symptoms of PFH through inactivating the sympathetic system.



中文翻译:

CHRNA1促进原发性局灶性多汗症的发病机制

该研究的目的是阐明胆碱能受体烟碱 α 1 亚基 (CHRNA1) 参与原发性局灶性多汗症 (PFH) 的发病机制。使用毛果芸香碱注射液构建多汗症小鼠模型。使用蛋白质印迹和定量实时 PCR (qRT-PCR) 分析比较 PFH 患者和多汗症小鼠汗腺组织中 CHRNA1 的表达水平。比较了用靶向 CHRNA1 (si-CHRNA1) 或非特异性 siRNA 的小干扰 RNA (siRNA) 治疗的多汗症小鼠的汗液分泌。使用透射电子显微镜检查多汗症小鼠汗腺细胞中的汗液分泌颗粒。使用酶联免疫吸附测定法测量血清乙酰胆碱水平,而与 PFH 相关的标志物、包括水通道蛋白 5 (AQP5) 和钙电压门控通道亚基 Alpha1 C (CACNA1C),使用免疫组织化学分析和蛋白质印迹进行评估。使用蛋白质印迹法定量多汗症小鼠交感神经节轴突中的脑源性神经营养因子 (BDNF) 和神经调节蛋白 1 (NRG-1)。CHRNA1 上调是 PFH 患者和多汗症小鼠汗腺的特征。沉默 CHRNA1 会减少多汗症小鼠的汗液分泌和汗液分泌颗粒的数量。siCHRNA1 降低了血清乙酰胆碱以及汗腺中 AQP5 和 CACNA1C 的表达。交感神经节轴突中的 BDNF1 和 NRG-1 水平也因 siCHRNA1 处理而减弱。

更新日期:2021-01-24
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