Akasaka Y, Fujita K, Ishikawa Y, Asuwa N, Inuzuka K, Ishihara M, Ito M, Masuda T, Akishima Y, Zhang L, Ito K, Ishii T
Second Department of Pathology, School of Medicine, Toho University, and the Department of Plastic and Reconstructive Surgery, Tokyo Medical College, Tokyo, Japan.
Wound Repair Regen. 2001 Nov-Dec;9(6):501-6. doi: 10.1046/j.1524-475x.2001.00501.x.
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.
近期研究表明，伤口愈合过程中细胞凋亡的调控在瘢痕形成及病理性瘢痕发展中具有重要意义。在本研究中，我们发现瘢痕疙瘩成纤维细胞可因其高度浓缩的染色质和离散的核碎片而被识别为凋亡细胞。为进一步揭示细胞凋亡现象，我们对瘢痕疙瘩手术切除组织（N = 10）、增生性瘢痕（N = 10）、正常愈合的扁平瘢痕（N = 10）及皮肤纤维瘤（N = 10）中末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）阳性细胞数量进行了量化。TUNEL阳性细胞数量相对较低，但瘢痕疙瘩组显著高于正常愈合的扁平瘢痕组（p = 0.004），提示瘢痕疙瘩成纤维细胞亚群中细胞存活率降低且凋亡细胞死亡增加。此外，瘢痕疙瘩组TUNEL阳性细胞数量显著高于皮肤纤维瘤组（p = 0.044），表明瘢痕疙瘩成纤维细胞亚群可能通过细胞死亡比皮肤纤维瘤更有效地抑制肿瘤发生。增生性瘢痕的凋亡水平显著高于正常愈合的扁平瘢痕（p = 0.033）。因此，这些结果提示瘢痕疙瘩和增生性瘢痕中的特定成纤维细胞会发生凋亡，这可能在病理性瘢痕形成过程中发挥作用。
