title: Nr1d1, an important circadian pathway regulatory gene, is suppressed by cigarette smoke in murine lungs.
abstract: Nuclear receptor subfamily 1, group D member 1 (Nr1d1), also known as Rev-erb-alpha, 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 approximately 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.
authors.affiliation: Department of Internal Medicine, Centre for Comparative Respiratory Biology and Medicine, University of California, Davis, CA 95616, USA. vtvasu@ucdavis.edu
authors.forename: Vihas T
authors.initials: VT
authors.lastname: Vasu
authors.forename: Carroll E
authors.initials: CE
authors.lastname: Cross
authors.forename: Kishorchandra
authors.initials: K
authors.lastname: Gohil
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012907:Smoking / Q000009:adverse effects*; D013045:Species Specificity
chemical_list: C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1