Telomere shortening may be associated with human keloids.
BACKGROUND
Keloids are benign skin tumors that are the effect of a dysregulated wound-healing process in genetically predisposed patients. They are inherited with an autosomal dominant mode with incomplete clinical penetrance and variable expression. Keloids are characterized by formation of excess scar tissue beyond the boundaries of the wound. The exact etiology is still unknown and there is currently no appropriate treatment for keloid disease.


METHODS
We analyzed sample tissues were obtained from 20 patients with keloid skin lesions and normal skin was obtained from 20 healthy donors. The telomeres were measured by Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay. Quantitative Real-Time RT-PCR analysis of hTERT gene expression was performed and intracellular ROS generation was measured.


RESULTS
In this study, we determined whether telomeric shortening and the expression of human telomerase reverse transcriptase (hTERT) occurs in keloid patients. Using Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay, we detected a significant telomere shortening of 30% in keloid specimens compared to normal skin. Using quantitative Real-Time RT-PCR, telomerase activity was found absent in the keloid tissues. Moreover, an increase in ROS generation was detected in fibroblasts cell cultures from keloid specimens as more time elapsed compared to fibroblasts from normal skin.


CONCLUSIONS
Telomere shortening has been reported in several metabolic and cardiovascular diseases. We found that telomere shortening can also be associated with human keloids. Chronic oxidative stress plays a major role in the pathophysiology of several chronic inflammatory diseases. Here we found increased ROS generation in fibroblasts from keloid fibroblasts cell cultures when compared to normal skin fibroblasts. Hence we conclude that oxidative stress might be an important modulator of telomere loss in keloid because of the absence of active telomerase that counteracts telomere shortening.
De Felice
Bruna
B
Department of Life Sciences, University of Naples II, Via Vivaldi 43, 81100 Caserta, Italy. bruna.defelice@unina2.it
Wilson
Robert R
RR
Nacca
Massimo
M
D000328:Adult; D015139:Blotting, Southern; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D056726:Genetic Association Studies; D006801:Humans; D007627:Keloid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D012150:Polymorphism, Restriction Fragment Length; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure
D017382:Reactive Oxygen Species; D019098:Telomerase