Document Detail


Defining the transcriptome of accelerated and replicatively senescent keratinocytes reveals links to differentiation, interferon signaling, and Notch related pathways.
MedLine Citation:
PMID:  16440318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epidermal keratinocytes (KCs) undergo highly orchestrated morphological and molecular changes during transition from proliferative compartment into growth arrested early and late differentiation layers, prior to dying in outermost cornified layers of normal skin. Creation of stratum corneum is vital to barrier function protecting against infection. Transcriptional events in KCs regulating complex processes of differentiation and host defense required to maintain constant epidermal thickness and resistance to infection in either young or aged skin are largely unknown. Furthermore, as terminal differentiation is characterized by irreversible loss of replicative potential culminating in dead layers at the skin surface, this process may be viewed as a form of senescence. However, a complete transcriptional profile of senescent (SN) human KCs has not been previously defined to permit delineation of molecular boundaries involving differentiation and senescence. To fill this void, we utilized global transcriptional analysis of KCs maintained in vitro as either cultures of proliferating (PR) cells, early and late confluent (LC) (accelerated senescence) cultures, or KCs undergoing replicative senescence. Global gene expression profiling revealed early confluent (EC) KCs were somewhat similar to PR KCs, while prominent differences were evident when compared to LC KCs; which were also distinct from replicatively SN KCs. While confluent KCs have in common several genes regulating differentiation with replicatively SN KCs, the latter cells expressed elevated levels of genes involved in interferon signaling and inflammatory pathways. These results provide new insights into cell autonomous transcriptional-based programs operative within KCs contributing to replicative senescence, with partial sharing of genes involved in differentiation. In addition, regulation of KC senescence may involve participation of interferon signaling pathways derived from the important role of KCs in protecting skin from infection. Integrating all of the transcriptional data revealed a key role for Notch receptor mediated signaling in the confluency induced differentiation phenotype using this model system.
Authors:
Ranjan J Perera; Seongjoon Koo; C Frank Bennett; Nicholas M Dean; Nitin Gupta; Jian-Zhong Qin; Brian J Nickoloff
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  98     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-12     Completed Date:  2006-07-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  394-408     Citation Subset:  IM    
Copyright Information:
Copyright 2006 Wiley-Liss, Inc.
Affiliation:
Keck Graduate Institute, Claremont, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics
Cell Aging / genetics,  physiology
Cell Differentiation / genetics*,  physiology
Cell Proliferation
Cells, Cultured / ultrastructure
Epidermis / anatomy & histology
Gene Expression Profiling
Genes, cdc / physiology
Humans
Interferons / metabolism
Keratinocytes / metabolism*,  ultrastructure*
Oligonucleotide Array Sequence Analysis / methods
Proteins / metabolism
Receptors, Notch / metabolism*
Reverse Transcription / genetics
Signal Transduction / genetics*
Transcription, Genetic / genetics*
Grant Support
ID/Acronym/Agency:
AR47307/AR/NIAMS NIH HHS; AR47814/AR/NIAMS NIH HHS; CA39542/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proteins; 0/Receptors, Notch; 9008-11-1/Interferons

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


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