Document Detail


Kruppel-like factor 5 is required for perinatal lung morphogenesis and function.
MedLine Citation:
PMID:  18599506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-03
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  135     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-14     Completed Date:  2008-09-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  2563-72     Citation Subset:  IM    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
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:
HL 061646/HL/NHLBI NIH HHS; HL 090156/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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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