Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle.

Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle.
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DOI:
10.1016/j.abb.2021.108897
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发表时间:
2021-07-30
影响因子:
3.9
通讯作者:
Pabelick CM
Pabelick CM
中科院分区:
生物学3区
文献类型:
--
作者:
Borkar NA;Roos B;Prakash YS;Sathish V;Pabelick CM

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哮喘等疾病会因炎症、香烟烟雾甚至电子烟等尼古丁输送装置而加剧。然而,目前关于尼古丁如何影响气道的信息很少,特别是在人类中,以及在炎症或哮喘背景下的变化。在这里,一个长期的假设是,气道平滑肌(ASM)是支气管收缩的关键,具有毒蕈碱受体,而烟碱受体(nAChR)只在气道神经元上。在这项研究中,我们验证了人ASM表达α 7 nAChR的假设,并使用非哮喘患者与轻中度哮喘患者的ASM探索其在炎症和哮喘中的分布。mRNA和Western分析显示,α7亚基在ASM细胞中表达最多,在哮喘患者和吸烟者中表达进一步增加,或暴露于尼古丁、香烟烟雾或促炎细胞因子TNFα和IL-13。在这些作用中,与哮喘相关的信号通路如NFκB B、AP-1和CREB B都参与其中。这些新的数据证实了α 7 nAChR在人ASM中的表达,并表明其在尼古丁暴露背景下在哮喘病理生理学中的潜在作用。
Diseases such as asthma are exacerbated by inflammation, cigarette smoke and even nicotine delivery devices such as e-cigarettes. However, there is currently little information on how nicotine affects airways, particularly in humans, and changes in the context of inflammation or asthma. Here, a longstanding assumption is that airway smooth muscle (ASM) that is key to bronchoconstriction has muscarinic receptors while nicotinic receptors (nAChRs) are only on airway neurons. In this study, we tested the hypothesis that human ASM expresses α7nAChR and explored its profile in inflammation and asthma using ASM of non-asthmatics vs. mild-moderate asthmatics. mRNA and western analysis showed the α7 subunit is most expressed in ASM cells and further increased in asthmatics and smokers, or by exposure to nicotine, cigarette smoke or pro-inflammatory cytokines TNFα and IL-13. In these effects, signaling pathways relevant to asthma such as NFκB, AP-1 and CREB are involved. These novel data demonstrate the expression of α7nAChR in human ASM and suggest their potential role in asthma pathophysiology in the context of nicotine exposure.
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