Document Detail


Defective induction of senescence during wound healing is a possible mechanism of keloid formation.
MedLine Citation:
PMID:  16278054     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Keloids are a hyperproliferative response of connective tissue in response to trauma. The mechanism by which this occurs is poorly understood and currently no successful treatment exists. Hypothesis: Senescent fibroblasts form during wound repair, as the result of oxidative stress. They have a major role in the control of fibroblast proliferation and extracellular matrix synthesis, acting as inhibitors. The defective induction of stress-induced senescent phenotype (SIPS) creates an insufficient number of senescent cells, diminishing the inhibitor effect, causing the uncontrolled hyperproliferation and keloid formation. In the proposed mechanism of keloid formation, fibroblasts have a major role, but it is also possible that other cells are involved, like keratinocytes and melanocytes. Accepting the hypothesis to be correct, a therapy that induces senescence can be used to prevent the keloid formation. Current therapies are only partially effective because they either induce senescence in too few cells or in enough number of cells, but at the same time inducing death (apoptosis and necrosis) of other cells. Dead cells are probably the source of a new repair cycle (proliferation), therefore the process of keloid formation is only postponed but not blocked. A more efficient prevention of keloid formation could be achieved using specific drugs or physical methods that induce senescence and not cell death. Therapies based on photodynamic and PUVA therapy, capable to induce predominantly cell senescence, can be possibly effective. The magnitude of oxidative stress, created during photodynamic therapy, can be reduced and used to produce sublethal doses, to cause senescence instead of cell death. Except standard photosensitizers, other drugs could be used, that are not so powerful in inducing oxidative stress, i.e. amphotericin B in combination with UV light.
Authors:
T Manestar Blazić; I Brajac
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Publication Detail:
Type:  Journal Article     Date:  2005-11-08
Journal Detail:
Title:  Medical hypotheses     Volume:  66     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  2006  
Date Detail:
Created Date:  2006-01-10     Completed Date:  2006-06-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  649-52     Citation Subset:  IM    
Affiliation:
Department of Dermatovenerology, Rijeka Medical School and University Hospital Center, Kresimirova 42, 510000 Rijeka, Croatia. teo.manestar.blazic@ri.t-com.hr
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MeSH Terms
Descriptor/Qualifier:
Amphotericin B / pharmacology
Apoptosis
Cell Aging
Cell Proliferation
Extracellular Matrix / metabolism
Fibroblasts / metabolism
Humans
Keloid / metabolism*,  pathology*,  therapy
Keratinocytes / metabolism
Melanocytes / metabolism
Necrosis / pathology
Photochemotherapy
Photosensitizing Agents
Ultraviolet Rays
Wound Healing*
Chemical
Reg. No./Substance:
0/Photosensitizing Agents; 1397-89-3/Amphotericin B

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


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