Circadian timing in the lung; a specific role for bronchiolar epithelial cells.
Circadian timing in the lung; a specific role for bronchiolar epithelial cells.
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DOI：
10.1210/en.2008-0638
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发表时间：
2009-01
期刊：
影响因子：
4.8
通讯作者：
Loudon AS
中科院分区：
文献类型：
--
作者：
Gibbs JE;Beesley S;Plumb J;Singh D;Farrow S;Ray DW;Loudon AS
除了位于视交叉上核内的核心昼夜节律振荡器之外，许多外周组织还拥有自我维持的昼夜节律计时器。在体内，这些由核心振荡器传送的信号夹带并在时间上同步。在本研究中，我们检查了肺部的昼夜节律，确定了小鼠和人类肺组织中核心时钟蛋白的细胞定位，并确定了糖皮质激素（广泛用于治疗哮喘）对肺时钟的影响。使用从转基因 mPER2::Luc 小鼠制备的器官型肺切片，在几天内测量报告 PER2 表达的荧光素酶水平。我们证明了小鼠肺部对糖皮质激素有反应的强大昼夜节律。使用免疫组织化学技术将核心时钟蛋白和糖皮质激素受体的特异性表达定位于小鼠和人肺中细支气管内壁的上皮细胞。在小鼠中，这些细胞被确定为克拉拉细胞。小鼠 Clara 细胞在培养中作为纯群体生长时保留了昼夜节律。此外，克拉拉细胞的选择性消融导致肺切片中昼夜节律的丧失，证明了这种细胞类型在维持整体肺昼夜节律方面的重要性。总之，我们证明克拉拉细胞对于维持肺组织中连贯的昼夜节律振荡至关重要。它们的糖皮质激素受体和核心时钟成分的共表达使它们成为体液视交叉上核输出和昼夜节律肺生理学之间的可能接口。
In addition to the core circadian oscillator, located within the suprachiasmatic nucleus, numerous peripheral tissues possess self-sustaining circadian timers. In vivo these are entrained and temporally synchronized by signals conveyed from the core oscillator. In the present study, we examine circadian timing in the lung, determine the cellular localization of core clock proteins in both mouse and human lung tissue, and establish the effects of glucocorticoids (widely used in the treatment of asthma) on the pulmonary clock. Using organotypic lung slices prepared from transgenic mPER2::Luc mice, luciferase levels, which report PER2 expression, were measured over a number of days. We demonstrate a robust circadian rhythm in the mouse lung that is responsive to glucocorticoids. Immunohistochemical techniques were used to localize specific expression of core clock proteins, and the glucocorticoid receptor, to the epithelial cells lining the bronchioles in both mouse and human lung. In the mouse, these were established to be Clara cells. Murine Clara cells retained circadian rhythmicity when grown as a pure population in culture. Furthermore, selective ablation of Clara cells resulted in the loss of circadian rhythm in lung slices, demonstrating the importance of this cell type in maintaining overall pulmonary circadian rhythmicity. In summary, we demonstrate that Clara cells are critical for maintaining coherent circadian oscillations in lung tissue. Their coexpression of the glucocorticoid receptor and core clock components establishes them as a likely interface between humoral suprachiasmatic nucleus output and circadian lung physiology.
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肺上皮对中性粒细胞弹性酶的敏感性：天然抑制剂的保护。
影响因子：
4.6
作者：
Bingle, L;Richards, R J;Fox, B;Masek, L;Guz, A;Tetley, T D
通讯作者：
Tetley, T D
影响因子：
56.9
作者：
Balsalobre, A;Brown, SA;Schibler, U
通讯作者：
Schibler, U
影响因子：
2.9
作者：
Okamoto, K;Onai, K;Ishiura, M
通讯作者：
Ishiura, M
DOI：
10.1152/ajplung.00024.2007
发表时间：
2007-08-01
影响因子：
4.9
作者：
Elizur, Arnon;Adair-Kirk, Tracy L.;Senior, Robert M.
通讯作者：
Senior, Robert M.
影响因子：
3.5
作者：
Guillaumond, F;Dardente, H;Cermakian, N
通讯作者：
Cermakian, N