Telomere shortening may be associated with human keloids.
Telomere shortening may be associated with human keloids.
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DOI：
10.1186/1471-2350-10-110
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发表时间：
2009-10-28
影响因子：
--
通讯作者：
Nacca M
中科院分区：
文献类型：
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作者：
De Felice B;Wilson RR;Nacca M
瘢痕疙瘩是一种良性皮肤肿瘤，是遗传倾向患者伤口愈合过程失调的结果。其遗传方式为常染色体显性遗传，临床外显性不全，表现多样。瘢痕疙瘩的特征是在伤口边界之外形成多余的疤痕组织。确切的病因尚不清楚，目前尚无治疗瘢痕疙瘩的适当方法。我们分析了20例瘢痕疙瘩患者的皮肤组织和20例健康供者的正常皮肤组织。用末端限制性片段分析(TRF)和实时荧光定量聚合酶链式反应(Real-Time-PCR)检测端粒。实时定量RT-PCR分析hTERT基因的表达，并测定细胞内ROS的产生。在这项研究中，我们确定了瘢痕疙瘩患者是否存在端粒缩短和人类端粒酶逆转录酶(HTERT)的表达。利用末端限制性片段(TRF)分析和实时定量聚合酶链式反应(Real-Time PCR)分析，我们检测到瘢痕疙瘩组织中端粒较正常皮肤明显缩短30%。实时荧光定量RT-PCR检测发现瘢痕疙瘩组织中端粒酶活性缺失。此外，与正常皮肤成纤维细胞相比，瘢痕疙瘩成纤维细胞培养的ROS生成随着时间的延长而增加。端粒缩短在几种代谢和心血管疾病中已有报道。我们发现端粒缩短也与人类瘢痕疙瘩有关。慢性氧化应激在几种慢性炎症性疾病的病理生理学中起主要作用。在这里，我们发现，与正常皮肤成纤维细胞相比，瘢痕疙瘩成纤维细胞培养的成纤维细胞产生更多的ROS。因此，我们得出结论，氧化应激可能是瘢痕疙瘩端粒丢失的一个重要调节因素，因为没有活性的端粒酶来抵消端粒缩短。
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. 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. 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. 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.