Dataset Information

Integrative sequence and tissue expression profiling of chicken and mammalian aquaporins.

ABSTRACT: Proteins that selectively transport water across the membranes of cells are recognized as important in the normal functioning of the body systems of vertebrates. There are 13 known mammalian aquaporins (AQP0 to AQP12), some of which have been shown to have unexpected cellular roles beyond transmembrane water transport. The availability of non-mammalian vertebrate animal models has the potential to provide insight into the emergence of diverse function in the aquaporins. The domesticated chicken (Gallus gallus) is the premier avian model for biological research; however, only a limited number of studies have compared chicken and mammalian aquaporins. The identification of aquaporins that share functional motifs or are expressed in the same tissues in human and chicken could allow the further functional analyses of homologous aquaporins in both species. We hypothesize that integrative analyses of protein sequences and body site expression of human, mouse, rat and chicken aquaporins has the potential to yield novel biological hypotheses about the unexpected cellular roles of aquaporins beyond transmembrane water transport.A total of 76 aquaporin transcript models derived from 47 aquaporin genes were obtained for human, mouse, rat and chicken. Eleven body sites (brain, connective tissue, head, heart, liver, muscle, ovary, pancreas, small intestine, spleen and testis) were identified in which there is suggested expression of at least one mammalian and one chicken aquaporin. This study demonstrates that modern on-line analysis tools, a novel matrix integration technique, and the availability of the chicken genome for comparative genomics and expression analysis enables hypothesis generation in several important areas including: (i) alternative transcription and speciation effects on the conservation of functional motifs in vertebrate aquaporins; (ii) the emergence of basolateral targeting in mammalian species; (iii) the potential of the cysteine-rich AQP11 as a possible target in the pathophysiology of neurodegenerative disorders such as autism that involve Purkinje cells; and (iv) possible impairment of function of pancreas-expressed AQP12 during pancreatotropic necrosis in avian influenza virus infection.The investigation of aquaporin function in chicken and mammalian species has the potential to accelerate the discovery of novel knowledge of aquaporins in both avian and mammalian species.

SUBMITTER: Isokpehi RD

PROVIDER: S-EPMC2966333 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Integrative sequence and tissue expression profiling of chicken and mammalian aquaporins.

Isokpehi Raphael D RD Rajnarayanan Rajendram V RV Jeffries Cynthia D CD Oyeleye Tolulola O TO Cohly Hari H P HH

BMC genomics 20090714

<h4>Background</h4>Proteins that selectively transport water across the membranes of cells are recognized as important in the normal functioning of the body systems of vertebrates. There are 13 known mammalian aquaporins (AQP0 to AQP12), some of which have been shown to have unexpected cellular roles beyond transmembrane water transport. The availability of non-mammalian vertebrate animal models has the potential to provide insight into the emergence of diverse function in the aquaporins. The do ...[more]

PMID: 19607658

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Project description:BackgroundExcessive accumulation of lipids in the adipose tissue is a major problem in the present-day broiler industry. However, few studies have analyzed the expression of adipose tissue genes that are involved in pathways and mechanisms leading to adiposity in chickens. Gene expression profiling of chicken adipose tissue could provide key information about the ontogenesis of fatness and clarify the molecular mechanisms underlying obesity. In this study, Chicken Genome Arrays were used to construct an adipose tissue gene expression profile of 7-week-old broilers, and to screen adipose tissue genes that are differentially expressed in lean and fat lines divergently selected over eight generations for high and low abdominal fat weight.ResultsThe gene expression profiles detected 13,234-16,858 probe sets in chicken adipose tissue at 7 weeks, and genes involved in lipid metabolism and immunity such as fatty acid binding protein (FABP), thyroid hormone-responsive protein (Spot14), lipoprotein lipase(LPL), insulin-like growth factor binding protein 7(IGFBP7) and major histocompatibility complex (MHC), were highly expressed. In contrast, some genes related to lipogenesis, such as leptin receptor, sterol regulatory element binding proteins1 (SREBP1), apolipoprotein B(ApoB) and insulin-like growth factor 2(IGF2), were not detected. Moreover, 230 genes that were differentially expressed between the two lines were screened out; these were mainly involved in lipid metabolism, signal transduction, energy metabolism, tumorigenesis and immunity. Subsequently, real-time RT-PCR was performed to validate fifteen differentially expressed genes screened out by the microarray approach and high consistency was observed between the two methods.ConclusionOur results establish the groundwork for further studies of the basic genetic control of growth and development of chicken adipose tissue, and will be beneficial in clarifying the molecular mechanism of obesity in chickens.

Project description:BackgroundA key step in the regulation of gene expression is the sequence-specific binding of transcription factors (TFs) to their DNA recognition sites. However, elucidating TF binding site (TFBS) motifs in higher eukaryotes has been challenging, even when employing cross-species sequence conservation. We hypothesized that for human and mouse, many orthologous genes expressed in a similarly tissue-specific manner in both human and mouse gene expression data, are likely to be co-regulated by orthologous TFs that bind to DNA sequence motifs present within noncoding sequence conserved between these genomes.ResultsWe performed automated motif searching and merging across four different motif finding algorithms, followed by filtering of the resulting motifs for those that contain blocks of information content. Applying this motif finding strategy to conserved noncoding regions surrounding co-expressed tissue-specific human genes allowed us to discover both previously known, and many novel candidate, regulatory DNA motifs in all 18 tissue-specific expression clusters that we examined. For previously known TFBS motifs, we observed that if a TF was expressed in the specified tissue of interest, then in most cases we identified a motif that matched its TRANSFAC motif; conversely, of all those discovered motifs that matched TRANSFAC motifs, most of the corresponding TF transcripts were expressed in the tissue(s) corresponding to the expression cluster for which the motif was found.ConclusionOur results indicate that the integration of the results from multiple motif finding tools identifies and ranks highly more known and novel motifs than does the use of just one of these tools. In addition, we believe that our simultaneous enrichment strategies helped to identify likely human cis regulatory elements. A number of the discovered motifs may correspond to novel binding site motifs for as yet uncharacterized tissue-specific TFs. We expect this strategy to be useful for identifying motifs in other metazoan genomes.

Project description:BackgroundTo study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue.MethodsThe AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-?CT method and correlated to clinicopathological parameters.ResultsTranscripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (??=?-?0.354; p =?0.013), D'Amico risk stratification (??=?-?0.336; p =?0.012), ISUP grade (??=?-?0.321; p =?0.017) and Gleason score (??=?-?0.342; p =?0.011).ConclusionsThis is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.

Dataset Information

Integrative sequence and tissue expression profiling of chicken and mammalian aquaporins.

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Integrative sequence and tissue expression profiling of chicken and mammalian aquaporins.

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