Document Detail


Sox2 activates cell proliferation and differentiation in the respiratory epithelium.
MedLine Citation:
PMID:  20855650     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sox2, a transcription factor critical for the maintenance of embryonic stem cells and induction of pluripotent stem cells, is expressed exclusively in the conducting airway epithelium of the lung, where it is required for differentiation of nonciliated, goblet, and ciliated cells. To determine the role of Sox2 in respiratory epithelial cells, Sox2 was selectively and conditionally expressed in nonciliated airway epithelial cells and in alveolar type II cells in the adult mouse. Sox2 induced epithelial cell proliferation within 3 days of expression. Epithelial cell proliferation was associated with increased Ki-67 and cyclin D1 staining. Expression of cell cycle genes, including FoxM1, Ccna2 (Cyclin A2), Ccnb2 (Cyclin B2), and Ccnd1 (Cyclin D1), was increased. Consistent with a role in cell proliferation, Sox2 activated the transcription of FoxM1 in vitro. In alveoli, Sox2 caused hyperplasia and ectopic differentiation of epithelial cells to those with morphologic and molecular characteristics of conducting airway epithelium. Sox2 induced the expression of conducting airway epithelial specific genes, including Scgb1a1, Foxj1, Tubb3, and Cyp2f2. Although prolonged expression of Sox2 caused cell proliferation and epithelial hyperplasia, Sox2 did not induce pulmonary tumors. Sox2 induces proliferation of respiratory epithelial cells and, subsequently, partially reprograms alveolar epithelial cells into cells with characteristics of the conducting airways.
Authors:
David H Tompkins; Valérie Besnard; Alexander W Lange; Angela R Keiser; Susan E Wert; Michael D Bruno; Jeffrey A Whitsett
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-20
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  45     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-13     Completed Date:  2011-09-08     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  101-10     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Differentiation / biosynthesis
Cell Cycle Proteins / biosynthesis
Cell Differentiation / physiology*
Cell Proliferation*
Epithelial Cells / cytology,  metabolism
Gene Expression Regulation / physiology
Mice
Mice, Transgenic
Pulmonary Alveoli / cytology,  metabolism*
Respiratory Mucosa / cytology,  metabolism*
SOXB1 Transcription Factors / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
HL090156/HL/NHLBI NIH HHS; HL099580/HL/NHLBI NIH HHS; R01 HL095580/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Differentiation; 0/Cell Cycle Proteins; 0/SOXB1 Transcription Factors; 0/Sox2 protein, mouse
Comments/Corrections

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