Differential Expression of Estrogen Receptor Variants in Response to Inflammation Signals in Human Airway Smooth Muscle
Differential Expression of Estrogen Receptor Variants in Response to Inflammation Signals in Human Airway Smooth Muscle
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DOI：
10.1002/jcp.25674
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发表时间：
2017-07-01
影响因子：
5.6
通讯作者：
Sathish, Venkatachalem
中科院分区：
文献类型：
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作者：
Aravamudan, Bharathi;Goorhouse, Katelyn J.;Sathish, Venkatachalem
青春期前和老年男性以及青春期后女性的哮喘患病率较高，这强烈表明性类固醇（尤其是雌激素）可能是肺部疾病的重要调节剂。我们最近证明，男性和女性的气道平滑肌（ASM）表达α和β形式的雌激素受体（ER和ER），并且这些受体调节细胞内[Ca2+]和ASM收缩性。尽管 ER 和 ER 都具有多个剪接变体，但尚不清楚这些变体的表达是否以及如何在慢性炎症/哮喘等条件下受到调节。为了检验 ER 和 ER 变体的差异表达有助于哮喘发病机制的假设，我们分析了哮喘和炎症（TNF 或 IL-13 治疗）ASM 中各种 ER 和 ER 基因的表达。在用 TNF (20ng/ml) 或 IL-13 (50ng/ml) 处理的哮喘 ASM 细胞或非哮喘细胞中评估 mRNA 和蛋白质水平的基因表达。我们观察到 ER 亚型的表达对炎症刺激的反应以及非哮喘 ASM 与哮喘 ASM 中的显着变化。 ER 和 ER 蛋白质水平的变化与观察到的差异 mRNA 模式相对应。药理学研究表明细胞质（p42/44 MAPK 和 PI3K）和细胞核（NFB、STAT6 和 AP-1）信号传导途径是介导和/或调节炎症对 ER 表达影响的假定机制。我们得出的结论是，ASM ER 表达谱的变化与炎症有关，并且 ER 变异可能有助于哮喘等气道疾病中的雌激素信号传导。 J.细胞。生理学。 232: 1754-1760, 2017。(c) 2016 Wiley periodicals, Inc.气道平滑肌细胞中 ER 同工型和变体的表达，以及这种表达在人气道平滑肌慢性炎症过程中是否以及如何改变。此外，还描述了炎症通过信号传导途径（例如细胞质和核信号传导）调节 ER 亚型的机制。
The prevalence of asthma is higher in pre-pubescent and aging males, and in post-pubertal females, strongly indicating that sex steroids (especially estrogen) may be an important modulator in lung disease. We recently demonstrated that airway smooth muscle (ASM) expresses both alpha and beta forms of the estrogen receptor (ER and ER) in males and females, and that these receptors regulate intracellular [Ca2+] and ASM contractility. Although both ER and ER have multiple splice variants, it is unclear if and how the expression of these variants is modulated under conditions such as chronic inflammation/asthma. In order to test the hypothesis that the differential expression of ER and ER variants contributes to the pathogenesis of asthma, we profiled the expression of various ER and ER genes in asthmatic and inflamed (TNF- or IL-13-treated) ASM. Gene expression was assessed at both the mRNA and protein levels in asthmatic ASM cells or non-asthmatic cells treated with TNF (20ng/ml) or IL-13 (50ng/ml). We observed marked variation in the expression of ER isoforms in response to inflammatory stimuli, and in non-asthmatic versus asthmatic ASM. Changes in protein levels of ER and ER corresponded with the observed differential mRNA patterns. Pharmacological studies implicate cytosolic (p42/44 MAPK and PI3K) and nuclear (NFB, STAT6, and AP-1) signaling pathways as putative mechanisms that mediate and/or regulate effects of inflammation on ER expression. We conclude that variations in ASM ER expression profiles occur with inflammation and that ER variants could contribute to estrogen signaling in airway diseases such as asthma. J. Cell. Physiol. 232: 1754-1760, 2017. (c) 2016 Wiley Periodicals, Inc.The expression of ER isoforms and variants in airway smooth muscle cells, and whether and how such expression is altered during chronic inflammation in human airway smooth muscle. In addition, the mechanism ER isoform modulation by inflammation via signaling pathways such as cytosolic as well as nuclear signaling also described.