Document Detail

Transcription factors Runx1 to 3 are expressed in the lacrimal gland epithelium and are involved in regulation of gland morphogenesis and regeneration.
MedLine Citation:
PMID:  23532528     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Lacrimal gland (LG) morphogenesis and repair are regulated by a complex interplay of intrinsic factors (e.g., transcription factors) and extrinsic signals (e.g., soluble growth/signaling factors). Many of these interconnections remain poorly characterized. Runt-related (Runx) factors belong to a small family of heterodimeric transcription factors known to regulate lineage-specific proliferation and differentiation of stem cells. The purpose of this study was to define the expression pattern and the role of Runx proteins in LG development and regeneration.
METHODS: Expression of epithelial-restricted transcription factors in murine LG was examined using immunostaining, qRT-PCR, and RT(2)Profiler PCR microarrays. The role of Runx transcription factors in LG morphogenesis was studied using siRNA and ex vivo LG cultures. Expression of Runx transcription factors during LG regeneration was assessed using in vivo model of LG regeneration.
RESULTS: We found that Runx factors are expressed in the epithelial compartment of the LG; in particular, Runx1 was restricted to the epithelium with highest level of expression in ductal and centroacinar cells. Downregulation of Runx1 to 3 expression using Runx-specific siRNAs abolished LG growth and branching and our data suggest that Runx1, 2, and 3 are partially redundant in LG development. In siRNA-treated LG, reduction of branching correlated with reduction of epithelial proliferation, as well as expression of cyclin D1 and the putative epithelial progenitor cell marker cytokeratin-5. Runx1, Runx3, and cytokeratin-5 expression increased significantly in regenerating LG and there was modest increase in Runx2 expression during LG differentiation.
CONCLUSIONS: Runx1 and 2 are new markers of the LG epithelial lineage and Runx factors are important for normal LG morphogenesis and regeneration.
Dmitry Voronov; Anastasia Gromova; Daren Liu; Driss Zoukhri; Alexander Medvinsky; Robyn Meech; Helen P Makarenkova
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-05-01
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-02     Completed Date:  2013-07-03     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3115-25     Citation Subset:  IM    
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MeSH Terms
Biological Markers
Cell Proliferation / drug effects
Core Binding Factor Alpha 1 Subunit / genetics*,  metabolism
Core Binding Factor Alpha 2 Subunit / genetics*,  metabolism
Core Binding Factor Alpha 3 Subunit / genetics*,  metabolism
Cyclin D1 / genetics,  metabolism
Epithelium / metabolism
Gene Expression Regulation / physiology*
Keratin-5 / genetics,  metabolism
Lacrimal Apparatus / embryology*,  metabolism*
Mice, Inbred BALB C
Mice, Inbred ICR
Mice, Knockout
Morphogenesis / physiology*
Organ Culture Techniques
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Real-Time Polymerase Chain Reaction
Regeneration / physiology*
Grant Support
1 R21 EY021292/EY/NEI NIH HHS; G0900962//Medical Research Council; R01-EY12383/EY/NEI NIH HHS; R21 EY021292/EY/NEI NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/Ccnd1 protein, mouse; 0/Core Binding Factor Alpha 1 Subunit; 0/Core Binding Factor Alpha 2 Subunit; 0/Core Binding Factor Alpha 3 Subunit; 0/Keratin-5; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Runx1 protein, mouse; 0/Runx2 protein, mouse; 0/Runx3 protein, mouse; 136601-57-5/Cyclin D1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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