The circadian clock regulates rhythmic erythropoietin expression in the murine kidney.
The circadian clock regulates rhythmic erythropoietin expression in the murine kidney.
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生物钟调节小鼠肾脏中节律性促红细胞生成素的表达
DOI：
10.1016/j.kint.2021.07.012
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发表时间：
--
影响因子：
19.6
通讯作者：
Dame C.
中科院分区：
文献类型：
--
作者：
Sciesielski LK;Felten M*;Michalick L*;Kirschner KM
Lattanzi G+;Jacobi CLJ+;Wallach T;Lang V;Landgraf D
Kramer A;Dame C.
昼夜节律的产生是细胞自主的，并且依赖于由包括CLOCK、BMAL 1和阻遏物如CLOCK 1和CLOCK 2的昼夜节律钟转录因子激活物家族控制的转录/翻译反馈环。本研究的目的是研究红细胞生成素昼夜表达的分子机制和造血意义。用核心昼夜节律钟基因隐花色素1和2（Cry-null）纯合缺失的突变小鼠来阐明促红细胞生成素的昼夜节律调节。野生型对照小鼠在昼夜节律时间06和18之间肾促红细胞生成素mRNA表达有显著差异。平行地，在昼夜节律时间18检测到肾脏中显著更高数量的促红细胞生成素产生细胞（通过RNAscope®）和显著更高水平的循环促红细胞生成素蛋白（通过ELISA）。这种变化在Cry基因敲除小鼠中被消除，并且独立于氧张力、氧饱和度或缺氧诱导因子2 α的表达，表明昼夜促红细胞生成素的表达受CRP 1和CRP 2的转录调控。报告基因分析表明，CLOCK/BMAL 1异源二聚体激活了5 '端促红细胞生成素启动子中的E-box元件。RNAscope®原位杂交证实了Bmal 1存在于肾脏的促红细胞生成素产生细胞中。在Cry-null小鼠中，发现网织红细胞数量显著减少，而红细胞数量和红细胞压积不变。因此，在含氧量正常的成年小鼠肾脏中，昼夜促红细胞生成素的调节是由昼夜节律激活因子CLOCK/BMAL 1和阻遏因子BLOCK 1/BLOCK 2转录控制的。这些发现可能对肾脏生理学和疾病，实验室诊断和贫血治疗有意义。
Generation of circadian rhythms is cell-autonomous and relies on a transcription/translation feedback loop controlled by a family of circadian clock transcription factor activators including CLOCK, BMAL1 and repressors such as CRY1 and CRY2. The aim of the present study was to examine both the molecular mechanism and the hemopoietic implication of circadian erythropoietin expression. Mutant mice with homozygous deletion of the core circadian clock genescryptochromes 1and2(Cry-null) were used to elucidate circadian erythropoietin regulation. Wild-type control mice exhibited a significant difference in kidneyerythropoietinmRNA expression between circadian times 06 and 18. In parallel, a significantly higher number of erythropoietin-producing cells in the kidney (by RNAscope®) and significantly higher levels of circulating erythropoietin protein (by ELISA) were detected at circadian time 18. Such changes were abolished inCry-null mice and were independent from oxygen tension, oxygen saturation, or expression ofhypoxia-inducible factor 2 alpha, indicating that circadian erythropoietin expression is transcriptionally regulated by CRY1 and CRY2. Reporter gene assays showed that the CLOCK/BMAL1 heterodimer activated an E-box element in the 5’erythropoietinpromoter. RNAscope®in situhybridization confirmed the presence ofBmal1in erythropoietin-producing cells of the kidney. InCry-null mice, a significantly reduced number of reticulocytes was found while erythrocyte numbers and hematocrit were unchanged. Thus, circadian erythropoietin regulation in the normoxic adult murine kidney is transcriptionally controlled by master circadian activators CLOCK/BMAL1, and repressors CRY1/CRY2. These findings may have implications for kidney physiology and disease, laboratory diagnostics, and anemia therapy.
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DOI：
10.1056/nejmra1802337
发表时间：
2021-02-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Allada R;Bass J
通讯作者：
Bass J
慢性阻塞性肺疾病血清促红细胞生成素循环水平的昼夜节律。
DOI：
--
发表时间：
1997
期刊：
Panminerva Medica (Testo stampato)
影响因子：
--
作者：
R. Casale;P. Pasqualetti
通讯作者：
P. Pasqualetti
人类真实和模拟微重力条件下的促红细胞生成素。
影响因子：
3.3
作者：
H. Gunga;K. Kirsch;F. Baartz;A. Maillet;C. Gharib;W. Nalishiti;I. Rich;L. Röcker
通讯作者：
L. Röcker
影响因子：
2.6
作者：
P. Wood;W. Hrushesky;R. Klevecz
通讯作者：
P. Wood;W. Hrushesky;R. Klevecz
人血清中促红细胞生成素的昼夜节律
影响因子：
6.5
作者：
L. Wide;C. Bengtsson And;G. Birgegarrd
通讯作者：
G. Birgegarrd