| Roles for β-catenin and doxycycline in the regulation of respiratory epithelial cell frequency and function. | |
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MedLine Citation:
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PMID: 21852686 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The expression of β-catenin-dependent genes can be increased through the Cre recombinase (Cre)-mediated elimination of the exon 3-encoded sequence. This mutant β-catenin is termed DE3, and promotes the expression of β-catenin-dependent genes. Our previous study used the DE3 model to demonstrate that persistent β-catenin activity inhibited bronchiolar Clara-to-ciliated cell differentiation. The present study was designed to evaluate the roles of β-catenin in regulating the tracheal progenitor cell hierarchy. However, initial experiments demonstrated that the tetracycline-responsive element-Cre transgene (TRE-Cre) was active in the absence of a reverse tetracycline transactivator driver or inducer, doxycycline (Dox). This spurious TRE-Cre transgene activity was not detected using the ROSA26-floxed STOP-LacZ reporter. To determine if the phenotype was a consequence of genotype or treatment with Dox, tracheal and lung specimens were evaluated using quantitative histomorphometric techniques. Analyses of uninduced mice demonstrated a significant effect of genotype on tracheal epithelial cell mass, involving basal, Clara-like cell types. The bronchial and bronchiolar Clara cell mass was also decreased. Paradoxically, an effect on ciliated cell mass was not detected. Activation of the β-catenin reporter transgene TOPGal demonstrated that β-catenin-dependent gene expression led to the genotype-dependent tracheal and bronchiolar phenotype. Comparative analyses of wild-type or keratin 14-rtTA(+/0)/TRE-cre(+/0)/DE3(+/+) mice receiving standard or Dox chow demonstrated an effect of treatment with Dox on basal, Clara-like, and Clara cell masses. We discuss these results in terms of cautionary notes and with regard to alterations of progenitor cell hierarchies in response to low-level injury. |
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Authors:
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Russell W Smith; Douglas A Hicks; Susan D Reynolds |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 46 ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-02-06 Completed Date: 2012-05-03 Revised Date: 2013-02-20 |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 115-24 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Animals Bronchi / drug effects, metabolism Cell Differentiation / drug effects, genetics Doxycycline / pharmacology* Epithelial Cells / cytology, drug effects, metabolism Gene Expression / drug effects, genetics Genotype Integrases Male Mice Phenotype Stem Cells / cytology, metabolism Tetracycline / pharmacology Trachea / cytology, drug effects*, metabolism* Trans-Activators / pharmacology Transgenes / drug effects, genetics beta Catenin / genetics, metabolism, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL075585-S1/HL/NHLBI NIH HHS; R01 HL075585/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Trans-Activators; 0/beta Catenin; 564-25-0/Doxycycline; 60-54-8/Tetracycline; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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