Document Detail

Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference.
MedLine Citation:
PMID:  17475244     Owner:  NLM     Status:  MEDLINE    
The intercellular adhesive junction desmosomes are essential for the maintenance of tissue structure and integrity in skin. Desmoplakin (Dp) is a major obligate plaque protein which plays a fundamental role in anchoring intermediate filaments to desmosomal cadherins. Evidence from hereditary human disease caused by mutations in the gene encoding Dp, e.g. Dp haploinsufficiency, suggests that alterations in Dp expression result not only in the disruption of tissue structure and integrity but also could evoke changes in keratinocyte proliferation. We have used transient RNA interference (RNAi) to downregulate Dp specifically in HaCaT keratinocytes. We showed that this Dp downregulation also caused reduced expression of several other desmosomal proteins. Increased cell proliferation and enhanced G(1)-to-S-phase entry in the cell cycle, as monitored by colonial cellular density and BrdU incorporation, were seen in Dp RNAi-treated cells. These proliferative changes were associated with elevated phospho-ERK1/2 and phospho-Akt levels. Furthermore, this increase in phospho-ERK/1/2 and phospho-Akt levels was sustained in Dp RNAi-treated cells at confluence whereas in control cells there was a significant reduction in phosphorylation of ERK1/2. This study indicates that Dp may participate in the regulation of keratinocyte cell proliferation by, in part at least, regulating cell cycle progression.
Hong Wan; Andrew P South; Ian R Hart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-30
Journal Detail:
Title:  Experimental cell research     Volume:  313     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-18     Completed Date:  2007-08-17     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2336-44     Citation Subset:  IM    
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MeSH Terms
Bromodeoxyuridine / metabolism
Cell Cycle / drug effects,  genetics*
Cell Proliferation / drug effects
Desmoplakins / antagonists & inhibitors,  genetics,  physiology*
Desmosomal Cadherins / metabolism
Desmosomes / drug effects,  genetics,  metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism
Keratinocytes / metabolism,  physiology*
Protein Precursors / metabolism
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
RNA, Small Interfering / pharmacology
Grant Support
G113/32//Medical Research Council
Reg. No./Substance:
0/Desmoplakins; 0/Desmosomal Cadherins; 0/Protein Precursors; 0/RNA, Small Interfering; 60108-77-2/involucrin; EC Proteins c-akt; EC Signal-Regulated MAP Kinases; G34N38R2N1/Bromodeoxyuridine

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