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Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma
Authors:YOSHIKIYO AKASAKA  MD  PhD  ;KAZUKO FUJITA  PhD  ;YUKIO ISHIKAWA  MD  PhD  ;NORIKO ASUWA  PhD  ;KIYOSHI INUZUKA  MD  PhD  ;MOTOKO ISHIHARA  MD  ;MASAMICHI ITO  MD  ;TAKAO MASUDA  MD  PhD  ;YURI AKISHIMA  MD  ;LIJUN ZHANG  ;KINJI ITO  MD  PhD  ;TOSHIHARU ISHII  MD  PhD
Institution:Second Department of Pathology, School of Medicine, Toho University, and the Department of Plastic and Reconstructive Surgery, Tokyo Medical College, Tokyo, Japan. akasakay@med.toho-u.ac.jp
Abstract:Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and the development of pathological scarring. In this study, we demonstrate that keloid fibroblasts can be identified as apoptotic cells because of their highly condensed chromatin and discrete nuclear fragments. To further reveal the phenomenon of apoptosis, we quantified the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in surgically resected tissues of keloids (N = 10), hypertrophic scars (N = 10), normal healed flat scars (N = 10), and dermatofibroma (N = 10). The number of TUNEL-positive cells was relatively low, but was significantly higher for the keloid group compared with the normally healed flat scar group (p = 0.004), suggesting reduced cell survival and increased apoptotic cell death in a subpopulation of keloid fibroblasts. Furthermore, the number of TUNEL-positive cells was significantly higher for the keloid group compared with the dermatofibroma group (p = 0.044), suggesting that a subpopulation of keloid fibroblasts may suppress tumorgenicity at a greater rate than dermatofibroma by undergoing cell death. Hypertrophic scars had significantly higher levels of apoptosis than normally healed flat scars (p = 0.033). Therefore, these results suggest that selected fibroblasts in keloids and hypertrophic scars undergo apoptosis, which may play a role in the process of pathological scarring.
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