Nr1d1, an important circadian pathway regulatory gene, is suppressed by cigarette smoke in murine lungs.
Nr1d1, an important circadian pathway regulatory gene, is suppressed by cigarette smoke in murine lungs.
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DOI：
10.1177/1534735409352027
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发表时间：
2009-12
影响因子：
2.9
通讯作者：
Gohil K
中科院分区：
文献类型：
--
作者：
Vasu VT;Cross CE;Gohil K
核受体亚家族1，D组成员1（Nr 1d 1），又称Rev-erb-α，属于“孤儿受体”家族，是生物钟基因家族的一员。除了是时钟电路的重要成员外，Nr 1d 1还调节细胞增殖、脂质代谢和炎症，并且还被誉为肿瘤抑制因子。我们对Nr 1d 1的关注受到了来自全基因组搜索的数据的刺激，这些数据是在肿瘤抗性C57 BL 6和肿瘤易感AJ小鼠品系中对香烟烟雾（CS）敏感的全烟（WS）和过滤烟雾（FS）-肺转录组的mRNA相关性。使用Affytek 430 A 2.0高密度寡核苷酸阵列对约15000个基因进行差异分析，确定了两种小鼠品系肺中CS对昼夜节律通路相关基因的调节。Nr 1d 1表达下调WS和FS无论小鼠品系相比，各自的空气呼吸控制。WS比FS更有效地降低Nr 1d 1的表达。目前的数据表明，CS的Nr 1d 1的转录调控可能会影响昼夜节律，从而可能在CS诱导的肺呼吸道病理生物学和/或肺肿瘤发生中发挥补充作用。
Nuclear receptor subfamily 1, group D member 1 (Nr1d1), also known as Rev-erb-α, belongs to the family of “orphan receptors” and functions as a member of clock gene family. In addition to being an important member of clock circuitry, Nr1d1, also regulates cell proliferation, lipid metabolism, and inflammation and is also touted as a tumor suppressor. Our focus on Nr1d1 was stimulated by data from a genome-wide search for mRNA correlates of cigarette smoke (CS) sensitive—whole smoke (WS) and filtered smoke (FS)—lung transcriptomes in tumor-resistant C57BL6 and tumor-susceptible AJ mice strains. Differential analysis of ~15 000 genes using Affymetrix 430A 2.0 high-density oligonucleotide arrays identified modulation of genes related to circadian pathways by CS in lungs of both mouse strains. Nr1d1 expression was downregulated by both WS and FS irrespective of mouse strain as compared to respective air-breathing controls. WS was more effective than FS on decreasing Nr1d1 expression. The present data suggest that transcriptional regulation of Nr1d1 by CS may affect circadian rhythmicity and thus may play a complementary role in CS-induced lung respiratory tract pathobiology and/or lung tumorigenesis.
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