Defining an olfactory receptor function in airway smooth muscle cells.
Defining an olfactory receptor function in airway smooth muscle cells.
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DOI：
10.1038/srep38231
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发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
An SS
中科院分区：
文献类型：
--
作者：
Aisenberg WH;Huang J;Zhu W;Rajkumar P;Cruz R;Santhanam L;Natarajan N;Yong HM;De Santiago B;Oh JJ;Yoon AR;Panettieri RA;Homann O;Sullivan JK;Liggett SB;Pluznick JL;An SS
控制或可用于改变哮喘中发生的气道平滑肌（ASM）质量增加和细胞重塑的途径尚未明确。在这里，我们报告的气味受体（ORs）属于超家族的G蛋白偶联受体（GPCR）的表达，以及典型的嗅觉机器（高尔夫和AC 3）在人支气管平滑肌。在分离的人ASM的原代培养物中，我们鉴定了多个OR的mRNA表达。引人注目的是，OR 51 E2是肺驻留细胞中映射到人类嗅觉组的最高度富集的OR转录物。在异源表达系统中，OR 51 E2很容易被运输到细胞表面，并显示出对短链脂肪酸（SCFAs）乙酸酯和丙酸酯的配体选择性和敏感性。肠道微生物群的这些内源性代谢副产物减缓了细胞骨架重塑的速率，以及人类ASM细胞的增殖。这些细胞反应在体外被发现在ASM从非哮喘患者和哮喘患者，并在OR 51 E2缺失的原代人ASM缺席。这些结果证明了ASM中的一种新的化学机械信号网络，并作为一个概念验证，即肠-肺轴的特异性受体可以靶向治疗哮喘中的气流阻塞。
Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma.
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气道平滑肌上的苦味受体通过局部钙信号传导和反向阻塞来支气管扩张。
影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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