Journal
MEDICAL HYPOTHESES
Volume 66, Issue 3, Pages 649-652Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.mehy.2005.09.033
Keywords
-
Categories
Ask authors/readers for more resources
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. (c) 2005 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available