Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma

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.

Normal and Pathologic Soft Tissue Remodeling: Role of the Myofibroblast, with Special Emphasis on Liver and Kidney Fibrosis

“…This latter proposition, however, lacks conclusive evidence to date. Recent papers have shown data supporting the possibility that there is increased survival of fibroblasts from keloid scars in response to signals that would normally induce apoptosis (Chodon et al, 2000;Ishihara et al, 2000), while other studies suggest a possible imbalance between proliferation and apoptosis in keloids and hypertrophic scars but without clear evidence of decreased levels of apoptosis (Akasawa et al, 2001;Luo et al, 2001). The expression of genes that are protective against apoptosis, such as Bcl-2, has been shown to be increased in keloids and hypertrophic scars, suggesting a mechanism through which an imbalance between proliferation and apoptosis may be achieved (Teofoli et al, 1999).…”

The effect of mitomycin-c in keloid fibroblast cultures

“…It has been known that extensive enlargement of keloid lesions is due to KF proliferations, collagen depositions, and cellular migrations. [3][4][5] In order to totally treat keloid lesions, we agree that MC must be combined with keloid surgery that removes the existing fibrous tissue material which richens by collagen bundles, such as previously reported by many authors. 15,16,22,23 In this combination, unremoving KF and collagen bundles on the surface of debulking lesions of preexisting keloid can be prevented to grow and to be prevented to relapse.…”

“…17 Our results showed that 120 uM MC can inhibit proliferation and migration of KF FIGURE 1. This finding is important because continuously enlargement of keloid lesion is under responsible of high proliferation rate of KF [3][4][5] and high migration ability to invade surrounding normal tissue. 8 Application 120 uM MC for 72 hours had no significantly different effect in proliferation index and inhibition of cellular migration than 24 hours.…”

“…1,2 This overgrowing is due to keloid fibroblast (KF) proliferation and producing collagen excessively [3][4][5] together with low activity of extracellular matrix metalloproteinase (MMP). 6,7 KF also have a characteristic of mesenchymal stem cells and can migrate to surrounding normal tissues to produce enlargement of fibrous tissues.…”

The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity

“…88 This process is also mediated in part by the induction of apoptosis, whereas in aberrant scarring, such as NVAMD, inadequate apoptosis may occur. [118][119][120] Similar to that in the earlier stages of repair, the bone marrow is also intrinsically involved in fibrogenesis. Fibrocytes in the peripheral blood are derived from mesenchymal stem cells in the bone marrow and are involved not only in scar tissue deposition but are also thought to have a role in the inflammatory and proliferative (NV) phases of repair.…”