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Molecular staging of epithelial maturation using secretory cell-specific genes as markers.

ABSTRACT: Bronchiolar Clara cells undergo phenotypic changes during development and in disease. These changes are poorly described due to a paucity of molecular markers. We used chemical and transgenic approaches to ablate Clara cells, allowing identification of their unique gene expression profile. Flavin monooxygenase 3 (Fmo3), paraoxonase 1 (Pon1), aldehyde oxidase 3 (Aox3), and claudin 10 (Cldn10) were identified as novel Clara cell markers. New and existing Clara cell marker genes were categorized into three classes based on their unique developmental expression pattern. Cldn10 was uniformly expressed in the epithelium at Embryonic Day (E)14.5 and became restricted to secretory cells at E18.5. This transition was defined by induction of CCSP. Maturation of secretory cells was associated with progressive increases in the expression of Fmo3, Pon1, Aox3, and Cyp2f2 between late embryonic and postnatal periods. Messenger RNA abundance of all categories of genes was dramatically decreased after naphthalene-induced airway injury, and displayed a sequence of temporal induction during repair that suggested sequential secretory cell maturation. We have defined a broader repertoire of Clara cell-specific genes that allows staging of epithelial maturation during development and repair.

SUBMITTER: Zemke AC

PROVIDER: S-EPMC2645532 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Molecular staging of epithelial maturation using secretory cell-specific genes as markers.

Zemke Anna C AC Snyder Joshua C JC Brockway Brian L BL Drake Jeffrey A JA Reynolds Susan D SD Kaminski Naftali N Stripp Barry R BR

American journal of respiratory cell and molecular biology 20080828 3

Bronchiolar Clara cells undergo phenotypic changes during development and in disease. These changes are poorly described due to a paucity of molecular markers. We used chemical and transgenic approaches to ablate Clara cells, allowing identification of their unique gene expression profile. Flavin monooxygenase 3 (Fmo3), paraoxonase 1 (Pon1), aldehyde oxidase 3 (Aox3), and claudin 10 (Cldn10) were identified as novel Clara cell markers. New and existing Clara cell marker genes were categorized in ...[more]

PMID: 18757308

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Project description:Ovarian cancer is a major cause of mortality in women. However, the molecular events underlying the pathogenesis of the disease are yet to be fully elucidated. In the present study, an integrated bioinformatics analysis was performed to identify core genes involved in serous epithelial ovarian cancer. A total of three expression datasets were downloaded from the Gene Expression Omnibus database, and included 46 serous epithelial ovarian cancer and 30 ovarian surface epithelium samples. The three datasets were merged, and batch normalization was performed. The normalized merged data were subsequently analyzed for differentially expressed genes (DEGs). In total, 2,212 DEGs were identified, including 1,300 upregulated and 912 downregulated genes. Gene Ontology analysis revealed that these DEGs were primarily involved in 'regulation of cell cycle', 'mitosis', 'DNA packaging' and 'nucleosome assembly'. The main cellular components included 'extracellular region part', 'chromosome', 'extracellular matrix' and 'condensed chromosome kinetochore', whereas the molecular functions included 'Calcium ion binding', 'polysaccharide binding', 'enzyme inhibitor activity', 'growth factor activity', 'cyclin-dependent protein kinase regulator activity', 'microtubule motor activity' and 'Wnt receptor activity'. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these DEGs were predominantly involved in 'Wnt signaling pathway', 'pathways in cancer', 'PI3K-Akt signaling pathway', 'cell cycle', 'ECM-receptor interaction', 'p53 signaling pathway' and 'focal adhesion'. The 20 most significant DEGs were identified from the protein-protein interaction network, and Oncomine analysis of these core genes revealed that 13 were upregulated and two were downregulated in serous epithelial ovarian cancer. Survival analysis revealed that cyclin B1, polo like kinase 1, G protein subunit γ transducin 1 and G protein subunit γ 12 are key molecules that may be involved in the prognosis of serous epithelial ovarian cancer. These core genes may provide novel treatment targets, although their roles in the carcinogenesis and prognosis of serous epithelial ovarian cancer require further study.

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Molecular staging of epithelial maturation using secretory cell-specific genes as markers.

Publications

Molecular staging of epithelial maturation using secretory cell-specific genes as markers.

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