| Kruppel-like factor 5 is required for perinatal lung morphogenesis and function. | |
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MedLine Citation:
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PMID: 18599506 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The transition to air breathing after birth requires both anatomic and biochemical maturation of the lung. Lung morphogenesis is mediated by complex paracrine interactions between respiratory epithelial cells and mesenchymal cells that direct transcriptional programs guiding patterning and cytodifferentiation of the lung. In the present study, transgenic mice were generated in which the Kruppel-like factor 5 gene (Klf5) was conditionally deleted in respiratory epithelial cells in the fetal lung. Lack of KLF5 inhibited maturation of the lung during the saccular stage of development. Klf5(Delta/Delta) mice died of respiratory distress immediately after birth. Abnormalities in lung maturation and morphogenesis were observed in the respiratory epithelium, the bronchiolar smooth muscle, and the pulmonary vasculature. Respiratory epithelial cells of both the conducting and peripheral airways were immature. Surfactant phospholipids were decreased and lamellar bodies, the storage form of surfactant, were rarely found. mRNA microarray analysis demonstrated that KLF5 influenced the expression of genes regulating surfactant lipid and protein homeostasis, vasculogenesis, including Vegfa, and smooth muscle cell differentiation. KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth. |
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Authors:
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Huajing Wan; Fengming Luo; Susan E Wert; Liqian Zhang; Yan Xu; Machiko Ikegami; Yutaka Maeda; Sheila M Bell; Jeffrey A Whitsett |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-07-03 |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 135 ISSN: 0950-1991 ISO Abbreviation: Development Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-07-14 Completed Date: 2008-09-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 2563-72 Citation Subset: IM |
Affiliation:
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Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Tumor Cell Proliferation Epithelial Cells / cytology, metabolism Gene Deletion Gene Expression Regulation, Developmental Genes, Reporter / genetics Genome / genetics Humans Kruppel-Like Transcription Factors / genetics, metabolism* Lipid Metabolism Lung / cytology, embryology*, metabolism* Mesoderm / embryology, metabolism Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Electron Morphogenesis* Pulmonary Surfactant-Associated Proteins / metabolism Transcription, Genetic / drug effects, genetics Transforming Growth Factor beta1 / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL 061646/HL/NHLBI NIH HHS; HL 090156/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Klf5 protein, mouse; 0/Kruppel-Like Transcription Factors; 0/Pulmonary Surfactant-Associated Proteins; 0/Transforming Growth Factor beta1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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