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Early gene expression in salivary gland after isoproterenol treatment.

ABSTRACT: Isoproterenol, a ?-adrenergic agonist, has been shown to induce salivary gland hyperplasia. However, the mechanism involved in this pharmacological phenomenon is not well understood. To gain a better understanding of the underlying changes, including genes, networks and pathways altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 min after isoproterenol injection. After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. Pathway analysis showed that cell hyperplasia, p38(MAPK), and IGF-1 were the most altered function, network and pathway, respectively. The balanced regulation of up- and down-expression of genes related to cell proliferation/survival may provide a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement without tumor transformation.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC4620551 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Early gene expression in salivary gland after isoproterenol treatment.

Zhou Yi Y Chen Hung-I H HI Lin A L AL Dang H H Haack Karin K Cole Shelley A SA Huang Yufei Y Yu Haiyang H Chen Yidong Y Yeh Chih-Ko CK

Journal of cellular biochemistry 20150301 3

Isoproterenol, a β-adrenergic agonist, has been shown to induce salivary gland hyperplasia. However, the mechanism involved in this pharmacological phenomenon is not well understood. To gain a better understanding of the underlying changes, including genes, networks and pathways altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 min after isoproterenol injection. After isoproterenol treatment, the number of differentially exp ...[more]

PMID: 25336019

Similar Datasets

Early gene expression in salivary gland after isoproterenol treatment

Project description:Isoproterenol, a β-adrenergic agonist, has been shown to induce salivary gland hyperplasia. To gain a better understanding of the underlying molecular changes altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 minutes after isoproterenol injection. After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. The regulation of up- and down-expression of genes related to cell proliferation/survival provides a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement.

2015-03-01 | GSE54965 | GEO

Early gene expression in salivary gland after isoproterenol treatment

Project description:Isoproterenol, a Î²-adrenergic agonist, has been shown to induce salivary gland hyperplasia. To gain a better understanding of the underlying molecular changes altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 minutes after isoproterenol injection. After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. The regulation of up- and down-expression of genes related to cell proliferation/survival provides a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement. For the time-course experiments, male Sprague-Dawley rats (2-3 months old) were injected intra-peritoneally with isoproterenol (20 mg/g body weight) or normal saline (control). The rats were euthanized at the indicated times and the harvested parotid glands stored at -80C until analyzed. Cells were harvested and processed at the following times: control (saline), immediately after treatment (10 min) and at 30 and 60min after treatment.

2015-03-01 | E-GEOD-54965 | biostudies-arrayexpress

Serial Analysis of Gene Expression in Plasmodium berghei salivary gland sporozoites.

Project description:BackgroundThe invasion of Anopheles salivary glands by Plasmodium sporozoites is an essential step for transmission of the parasite to the vertebrate host. Salivary gland sporozoites undergo a developmental programme to express genes required for their journey from the site of the mosquito bite to the liver and subsequent invasion of, and development within, hepatocytes. A Serial Analysis of Gene Expression was performed on Anopheles gambiae salivary glands infected or not with Plasmodium berghei and we report here the analysis of the Plasmodium sporozoite transcriptome.ResultsAnnotation of 530 tag sequences homologous to Plasmodium berghei genomic sequences identified 123 genes expressed in salivary gland sporozoites and these genes were classified according to their transcript abundance. A subset of these genes was further studied by quantitative PCR to determine their expression profiles. This revealed that sporozoites modulate their RNA amounts not only between the midgut and salivary glands, but also during their storage within the latter. Among the 123 genes, the expression of 66 is described for the first time in sporozoites of rodent Plasmodium species.ConclusionThese novel sporozoite expressed genes, especially those expressed at high levels in salivary gland sporozoites, are likely to play a role in Plasmodium infectivity in the mammalian host.

| S-EPMC2263065 | biostudies-literature

IL-22 regulation of functional gene expression in salivary gland cells.

Project description:TH17 cells and their associated signature cytokines, IL-17 and IL-22, are highly elevated in primary Sjögren's syndrome (pSjS). The levels of IL-22 present in sera showed significant correlations with many disease parameters, specifically hyposalivation, anti-SSB, anti-SSA/SSB, hypergammaglobulinemia and rheumatoid factor. The present study aims to examine the biological function of IL-22 on human salivary glands. To accomplish the goal, microarray analysis using the HumanHT-12 v4 Expression BeadChip was utilized to determine the biological function of IL-22. Differential expression analyses were conducted using the LIMMA package from the Bioconductor project. MTT assay, flow cytometry and Western blotting were used to identify the function of IL-22 on human salivary gland cells. Results indicate an extensive effect of IL-22 on many major molecular functions including activation of antimicrobial genes and downregulation of immune-associated pathways. Functional studies performed in-vitro using human salivary gland cells treated with IL-22 indicated a direct effect of IL-22 on cell cycling, specifically reducing cellular proliferation at the G2-M phase by activation of STAT3. These results suggest the important role of IL-22 in the salivary gland function. The present study suggests that IL-22 might be involved in regulating inflammation and controlling the cell proliferation in SjS.

| S-EPMC4778602 | biostudies-literature

Salivary gland gene expression atlas identifies a new regulator of branching morphogenesis.

Project description:During organ development, local changes in gene expression govern morphogenesis and cell fate. We have generated a microanatomical atlas of epithelial gene expression of embryonic salivary glands. The mouse submandibular salivary gland first appears as a single mass of epithelial cells surrounded by mesenchyme, and it undergoes rapid branching morphogenesis to form a complex secretory organ with acini connected to an extensive ductal system. Using laser capture microdissection, we collected samples from 14 distinct epithelial locations at embryonic days 12.5, 13.5, 14, and 15, and characterized their gene expression by microarray analysis. These microarray results were evaluated by qPCR of biological replicates and by comparisons of the gene expression dataset with published expression data. Using this gene expression atlas to search for novel regulators of branching morphogenesis, we found a substantial reduction in mRNA levels of GSK3β at the base of forming clefts. This unexpected finding was confirmed by immunostaining, and inhibition of GSK3β activity enhanced salivary gland branching. This first microanatomical expression atlas of a developing gland characterizes changes in local gene expression during salivary gland development and differentiation, which should facilitate the identification of key genes involved in tissue morphogenesis.

| S-EPMC3318080 | biostudies-literature

Promising Gene Therapeutics for Salivary Gland Radiotoxicity.

Project description:More than 0.5 million new cases of head and neck cancer are diagnosed worldwide each year, and approximately 75% of them are treated with radiation alone or in combination with other cancer treatments. A majority of patients treated with radiotherapy develop significant oral off-target effects because of the unavoidable irradiation of normal tissues. Salivary glands that lie within treatment fields are often irreparably damaged and a decline in function manifests as dry mouth or xerostomia. Limited ability of the salivary glands to regenerate lost acinar cells makes radiation-induced loss of function a chronic problem that affects the quality of life of the patients well beyond the completion of radiotherapy. The restoration of saliva production after irradiation has been a daunting challenge, and this review provides an overview of promising gene therapeutics that either improve the gland's ability to survive radiation insult, or alternately, restore fluid flow after radiation. The salient features and shortcomings of each approach are discussed.

| S-EPMC5345936 | biostudies-literature

Toward gene therapy for growth hormone deficiency via salivary gland expression of growth hormone.

Project description:ObjectivesSalivary glands are useful targets for gene therapeutics. After gene transfer into salivary glands, regulated secretory pathway proteins, such as human growth hormone, are secreted into saliva, whereas constitutive secretory pathway proteins, such as erythropoietin, are secreted into the bloodstream. Secretion of human growth hormone (hGH) into the saliva is not therapeutically useful. In this study, we attempted to redirect the secretion of transgenic hGH from the saliva to the serum by site-directed mutagenesis.Materials and methodsWe tested hGH mutants first in vitro with AtT20 cells, a model endocrine cell line that exhibits polarized secretion of regulated secretory pathway proteins. Selected mutants were further studied in vivo using adenoviral-mediated gene transfer to rat submandibular glands.ResultsWe identified two mutants with differences in secretion behavior compared to wild-type hGH. One mutant, ΔN1-6 , was detected in the serum of transduced rats, demonstrating that expression of this mutant in the salivary gland resulted in its secretion through the constitutive secretory pathway.ConclusionThis study demonstrates that mutagenesis of therapeutic proteins normally destined for the regulated secretory pathway may result in their secretion via the constitutive secretory pathway into the circulation for potential therapeutic benefit.

| S-EPMC4050033 | biostudies-literature

Global analysis of gene expression profiles in the submandibular salivary gland of klotho knockout mice.

Project description:Salivary dysfunction commonly occurs in many older adults and is considered a physiological phenomenon. However, the genetic changes in salivary glands during aging have not been characterized. The present study analyzed the gene expression profile in salivary glands from accelerated aging klotho deficient mice (klotho-/-, 4 weeks old). Microarray analysis showed that 195 genes were differentially expressed (z-score?>?2 in two independent arrays) in klotho null mice compared to wild-type mice. Importantly, alpha2-Na+ /K+ -ATPase (Atp1a2), Ca2+ -ATPase (Atp2a1), epidermal growth factor (EGF), and nerve growth factor (NGF), which have been suggested to be regulators of submandibular salivary gland function, were significantly decreased. When a network was constructed from the differentially expressed genes, proliferator-activated receptor-? (PPAR ?), which regulates energy homeostasis and insulin sensitivity, was located at the core of the network. In addition, the expression of genes proposed to regulate various PPAR ?-related cellular pathways, such as Klk1b26, Egfbp2, Cox8b, Gpx3, Fabp3, EGF, and NGF?, was altered in the submandibular salivary glands of klotho-/- mice. Our results may provide clues for the identification of novel genes involved in salivary gland dysfunction. Further characterization of these differentially expressed genes will be useful in elucidating the genetic basis of aging-related changes in the submandibular salivary gland.

| S-EPMC5765504 | biostudies-literature

Gene expression screening of salivary gland neoplasms: molecular markers of potential histogenetic and clinical significance.

Project description:Salivary gland neoplasms comprise phenotypically and biologically diverse lesions of uncertain histogenesis. The molecular events associated with their development and clinicopathological heterogeneity remain unknown. To reveal these events, we performed microarray expression analysis using a nylon-filter membrane platform on 18 primary lesions representing the most common benign and malignant types. Our study identified a small set of genes that are differentially altered between normal salivary gland tissues and benign and malignant tumors. Of the 5000 genes arrayed, 136 genes were differentially expressed by normal tissue, benign tumors, and various malignant neoplasms. Hierarchical clustering analysis differentiated between adenoid cystic carcinomas (ACCs) and other malignant subtypes. Non-ACC specimens manifested overlapping patterns of gene expression within and between tumors. Most of the differentially expressed genes share functional similarities with members of the adhesion, proliferation, and signal transduction pathways. Our study identified: 1) a set of genes that differentiate normal tissue from tumor specimens, 2) genes that differentiate pleomorphic adenoma and ACCs from other malignant salivary gland neoplasms, and 3) different patterns of expression between ACCs arising from major and minor salivary gland sites. The differentially expressed genes provide new information on potential genetic events of biological significance in future studies of salivary gland tumorigenesis.

| S-EPMC1867638 | biostudies-literature

Efficient Gene Knockout in Salivary Gland Epithelial Explant Cultures.

Project description:We have developed methods to achieve efficient CRISPR-Cas9-mediated gene knockout in ex vivo mouse embryonic salivary epithelial explants. Salivary epithelial explants provide a valuable model for characterizing cell signaling, differentiation, and epithelial morphogenesis, but research has been limited by a paucity of efficient gene perturbation methods. Here, we demonstrate highly efficient gene perturbation by transient transduction of guide RNA-expressing lentiviruses into Cas9-expressing salivary epithelial buds isolated from Cas9 transgenic mice. We first show that salivary epithelial explants can be cultured in low-concentration, nonsolidified Matrigel suspensions in 96-well plates, which greatly increases sample throughput compared to conventional cultures embedded in solidified Matrigel. We further show that salivary epithelial explants can grow and branch with FGF7 alone, while supplementing with insulin, transferrin, and selenium (ITS) enhances growth and branching. We then describe an efficient workflow to produce experiment-ready, high-titer lentiviruses within 1 wk after molecular cloning. To track transduced cells, we designed the lentiviral vector to coexpress a nuclear fluorescent reporter with the guide RNA. We routinely achieved 80% transduction efficiency when antibiotic selection was used. Importantly, we detected robust loss of targeted protein products when testing 9 guide RNAs for 3 different genes. Moreover, targeting the β1 integrin gene (Itgb1) inhibited branching morphogenesis, which supports the importance of cell-matrix adhesion in driving branching morphogenesis. In summary, we have established a lentivirus-based method that can efficiently perturb genes of interest in salivary epithelial explants, which will greatly facilitate studies of specific gene functions using this system.

| S-EPMC9893391 | biostudies-literature

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