Document Detail


Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference.
MedLine Citation:
PMID:  17475244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hong Wan; Andrew P South; Ian R Hart
Related Documents :
8843974 - The behavior of cells during the evaluation of gap junctional intercellular communicati...
12352684 - Functional study of gjb2 in hereditary hearing loss.
8887664 - Perturbations in the spi1p gtpase cycle of schizosaccharomyces pombe through its gtpase...
17241434 - Location of proliferating gingival cells following toothbrushing stimulation.
8457874 - Differentiation of neurogenic precursors within the neural crest cell lineage.
19429254 - Effects of an epidermal growth factor receptor inhibitor on arsenic associated toxicity...
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Bromodeoxyuridine / metabolism
Cell Cycle / drug effects,  genetics*
Cell Proliferation / drug effects
Desmoplakins / antagonists & inhibitors,  genetics,  physiology*
Desmosomal Cadherins / metabolism
Desmosomes / drug effects,  genetics,  metabolism
Down-Regulation
Extracellular Signal-Regulated MAP Kinases / metabolism
Humans
Keratinocytes / metabolism,  physiology*
Phosphorylation
Protein Precursors / metabolism
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
RNA, Small Interfering / pharmacology
Grant Support
ID/Acronym/Agency:
G113/32//Medical Research Council
Chemical
Reg. No./Substance:
0/Desmoplakins; 0/Desmosomal Cadherins; 0/Protein Precursors; 0/RNA, Small Interfering; 60108-77-2/involucrin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; G34N38R2N1/Bromodeoxyuridine

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


Previous Document:  Role of phosphatidylinositol-4-phosphate 5' kinase (ppk-1) in ovulation of Caenorhabditis elegans.
Next Document:  Identification and characterization of cells with high angiogenic potential and transitional phenoty...