Asthma and sarcoplasmic reticulum Ca2+ reuptake in airway smooth muscle.
Asthma and sarcoplasmic reticulum Ca2+ reuptake in airway smooth muscle.
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哮喘与气道平滑肌肌浆网 Ca2 再摄取。
DOI：
10.1152/ajplung.00237.2009
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Sieck,GaryC
中科院分区：
文献类型：
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作者：
Prakash,YS;Sathish,Venkatachalem;Thompson,MichaelA;Pabelick,ChristinaM;Sieck,GaryC
哮喘中气道过度狭窄涉及 ASM 收缩性增强和气道重塑 (1)。细胞内 Ca2+([Ca2+] i) 调节是 ASM 收缩性的关键，其中肌浆网 Ca2+ 释放和再摄取是重要组成部分。 SERCA 是补充肌浆网 (SR) Ca2+ 储备的主要机制。我们最近的研究基于暴露于促炎细胞因子的健康 ASM 细胞，表明哮喘中观察到的 ASM [Ca2+] i 增加可能是通过抑制 SERCA 表达和功能介导的。 Mahn 等人 (2) 的研究表明，与来自健康受试者的 ASM 相比，来自哮喘患者的 ASM 表达的 SERCA 量较低，但增殖和分泌较多（气道重塑的特征）。此外，后一组 ASM 中 SERCA 表达的抑制[使用小干扰 RNA (siRNA)] 模拟了哮喘 ASM 的更大增殖和分泌。我们的研究发现，即使是短期（过夜）接触细胞因子也会抑制 SERCA 并减慢 [Ca2+] i 对激动剂的反应，而 Mahn 等人的研究 (2) 在哮喘 ASM 中发现了类似的 [Ca2+] i 反应（其中 SERCA 表达降低）。因此，这两项研究将 SERCA 与哮喘中 ASM 改变的两个组成部分联系起来：收缩性和重塑。然而，我们的结果 (3) 表明，在哮喘 ASM (2) 中观察到的 SERCA 表达降低可能在气道炎症后相当早的时间内发生（即，甚至在重塑发生之前），并且这种状态可能随着疾病进展而维持。在这里，细胞因子（可能源自重塑 ASM）可能会随着时间的推移而改变作用，从一开始就改变 [Ca2+] i 和强制调节蛋白的表达，并进展到气道重塑。这两项研究都为未来的研究提出了一个有趣的问题：[Ca2+]i 升高是否是由于 SERCA（由细胞因子诱导）减少导致气道高反应性和重塑，或者 SERCA 表达减少是否是炎症诱导的更近端信号变化的标志？
Exaggerated airway narrowing in asthma involves both enhanced ASM contractility and airway remodeling (1). Intracellular Ca2+([Ca2+] i) regulation is key to ASM contractility, with sarcoplasmic reticulum Ca2+ release and reuptake being important components. SERCA is the major mechanism for replenishing sarcoplasmic reticulum (SR) Ca2+ stores. Our recent study, based on healthy ASM cells exposed to proinflammatory cytokines, suggests that the increase in ASM [Ca2+] i observed in asthma may be mediated by suppressed SERCA expression and function. The study by Mahn et al.(2) shows that ASM derived from asthmatics express lower amounts of SERCA but greater proliferation and secretion (features of airway remodeling) compared with ASM from healthy subjects. Furthermore, suppression of SERCA expression [using small interfering RNAs (siRNAs)] in ASM from the latter group mimics the greater proliferation and secretion of asthmatic ASM. Whereas our study found that even shortterm (overnight) exposure to cytokines suppresses SERCA and slows [Ca2+] i responses to agonist, the study by Mahn et al.(2) found similar [Ca2+] i responses in asthmatic ASM (where SERCA expression was decreased). Thus the two studies link SERCA to both components of altered ASM in asthma: contractility and remodeling. However, our results (3) suggest that the decreased SERCA expression observed in asthmatic ASM (2) may occur fairly early following airway inflammation (ie, even before remodeling occurs), and this status may be maintained with disease progression. Here, cytokines (potentially derived from the remodeling ASM) may have changing roles over time, with altered expression of [Ca2+] i and force regulatory proteins at the outset, progressing to airway remodeling. Both studies raise an intriguing question for future research: is it elevated [Ca2+] i resulting from decreased SERCA (induced by cytokines) that contributes to airway hyperreactivity and remodeling, or is decreased SERCA expression a marker of more proximal signaling changes induced by inflammation?
DOI：
10.1152/ajplung.00026.2009
发表时间：
2009-07-01
影响因子：
4.9
作者：
Sathish, Venkatachalem;Thompson, Michael A.;Sieck, Gary C.
通讯作者：
Sieck, Gary C.
DOI：
10.1073/pnas.0902295106
发表时间：
2009-06-30
影响因子：
11.1
作者：
Mahn, Katharina;Hirst, Stuart J.;Lee, Tak H.
通讯作者：
Lee, Tak H.