Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action
ABSTRACT Diurnal-nocturnal, or circadian-like, rhythms are 24-h variations in biological processes, evolved for the efficient functioning of living organisms. Such oscillations and their regulation in many peripheral tissues are still unclear. In this study, we used Affymetrix gene chips in a rich time-series experiment involving 54 animals killed at 18 time points within the 24-h cycle to examine light-dark cycle patterns of gene expression in rat lungs. Data mining identified 646 genes (represented by 1,006 probe sets) showing robust oscillations in expression in lung that were parsed into 8 distinct temporal clusters. Surprisingly, more than two-thirds of the probe sets showing cyclic expression peaked during the animal's light/inactive period. Six core clock genes and nine clock-related genes showed rhythmic oscillations in their expression in lung. Many of the genes that peaked during the inactive period included genes related to extracellular matrix, cytoskeleton, and protein processing and trafficking, which appear to be mainly involved in the repair and remodeling of the organ. Genes coding for growth factor ligands and their receptors, which play important roles in maintaining normal lung function, also showed rhythmic expression. In addition, genes involved in the metabolism and transport of endogenous compounds, xenobiotics, and therapeutic drugs, along with genes that are biomarkers or potential therapeutic targets for many lung diseases, also exhibited 24-h cyclic oscillations, suggesting an important role for such rhythms in regulating various aspects of the physiology and pathophysiology of lung.
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- "The consequences of frequent jetlag have serious effects on health, including sleep disorders, chronic memory deficits, obesity, diabetes, and other metabolic diseases  , as well as the development of cancer . Various chronomic studies [6–8, 13–15] seek to understand the endogenous and exogenous mechanisms of synchronization and desynchronization. "
ABSTRACT: Bioinformatics and other well-established sciences, such as molecular biology, genetics, and biochemistry, provide a scientific approach for the analysis of data generated through "omics" projects that may be used in studies of chronobiology. The results of studies that apply these techniques demonstrate how they significantly aided the understanding of chronobiology. However, bioinformatics tools alone cannot eliminate the need for an understanding of the field of research or the data to be considered, nor can such tools replace analysts and researchers. It is often necessary to conduct an evaluation of the results of a data mining effort to determine the degree of reliability. To this end, familiarity with the field of investigation is necessary. It is evident that the knowledge that has been accumulated through chronobiology and the use of tools derived from bioinformatics has contributed to the recognition and understanding of the patterns and biological rhythms found in living organisms. The current work aims to develop new and important applications in the near future through chronobiology research.The Scientific World Journal 09/2013; 2013:153839. DOI:10.1155/2013/153839 · 1.73 Impact Factor
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- "It has recently become apparent that there are strong links between metabolic functions and the circadian clock, with a relatively high percentage (20%) of the adipose transcriptome influenced by the circadian clock (Dallmann and Weaver, 2010; Johnston, 2012). Furthermore, the physiological functions of vital organs (e.g., lung, liver) are also dependent on or modulated by the circadian clock (Miller et al., 2007; Vollmers et al., 2009; Sukumaran et al., 2011). "
ABSTRACT: Fully mature enamel is about 98% mineral by weight. While mineral crystals appear very early during its formative phase, the newly secreted enamel is a soft gel-like matrix containing several enamel matrix proteins of which the most abundant is amelogenin (Amelx). Histological analysis of mineralized dental enamel reveals markings called cross-striations associated with daily increments of enamel formation, as evidenced by injections of labeling dyes at known time intervals. The daily incremental growth of enamel has led to the hypothesis that the circadian clock might be involved in the regulation of enamel development. To identify daily rhythms of clock genes and Amelx, we subjected murine ameloblast cells to serum synchronization to analyze the expression of the circadian transcription factors Per2 and Bmal1 by real-time PCR. Results indicate that these key genetic regulators of the circadian clock are expressed in synchronized murine ameloblast cell cultures and that their expression profile follows a circadian pattern with acrophase and bathyphase for both gene transcripts in antiphase. Immunohistological analysis confirms the protein expression of Bmal and Cry in enamel cells. Amelx expression in 2-day postnatal mouse molars dissected every 4 hours for a duration of 48 hours oscillated with an approximately 24-hour period, with a significant approximately 2-fold decrease in expression during the dark period compared to the light period. The expression of genes involved in bicarbonate production (Car2) and transport (Slc4a4), as well as in enamel matrix endocytosis (Lamp1), was greater during the dark period, indicating that ameloblasts express these proteins when Amelx expression is at the nadir. The human and mouse Amelx genes each contain a single nonconserved E-box element within 10 kb upstream of their respective transcription start sites. We also found that within 2 kb of the transcription start site of the human NFYA gene, which encodes a positive regulator of amelogenin, there is an E-box element that is conserved in rodents and other mammals. Moreover, we found that Nfya expression in serum-synchronized murine ameloblasts oscillated with a strong 24-hour rhythm. Taken together, our data support the hypothesis that the circadian clock temporally regulates enamel development.Journal of Biological Rhythms 06/2012; 27(3):237-45. DOI:10.1177/0748730412442830 · 3.32 Impact Factor
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ABSTRACT: With rapid accumulation of functional relationships between biological molecules, knowledge-based networks have been constructed and stocked in many databases. These networks provide the curated and comprehensive information for the functional linkages among genes and proteins, while their activities are highly related with specific phenotypes and conditions. To evaluate a knowledge-based network in a specific condition, measuring the consistency between its structure and the conditionally specific gene expression profiling data is an important criterion. In this work, we propose a Gaussian graphical model to evaluate the documented regulatory networks by the consistency between network architectures and time-series gene expression profiles. By developing a dynamical Bayesian network model, we derive a new method to evaluate gene regulatory networks in both simulated and true time series microarray data. The regulatory networks are evaluated by matching a network structure and gene expressions, which are achieved by randomly rewiring the regulatory structures. To demonstrate the effectiveness of our method, we identify the significant regulatory networks in response to the time series gene expression of circadian rhythm. Moreover, the knowledge-based networks are screened and ranked by their consistencies of structures based on dynamical gene expressions.Systems Biology (ISB), 2012 IEEE 6th International Conference on; 01/2012