PDF(Pubmed)
Abstract：
Keloid scars and folliculitis keloidalis nuchae (FKN) are benign fibroproliferative dermal lesions of unknown aetiology and ill-defined treatment, which typically present in genetically susceptible individuals. Their pathognomonic hallmarks include local aggressive invasive behaviour plus high recurrence post-therapy. In view of this, we investigated proliferative and key parameters of bioenergetic cellular characteristics of site-specific keloid-derived fibroblasts (intra(centre)- and peri(margin)-lesional) and FKN compared to normal skin and normal flat non-hypertrophic scar fibroblasts as negative controls.The results showed statistically significant (P < 0.01) and variable growth dynamics with increased proliferation and migration in keloid fibroblasts, while FKN fibroblasts showed a significant (P < 0.001) increase in proliferation but similar migration profile to controls. A statistically significant metabolic switch towards aerobic glycolysis in the fibroblasts from the disease conditions was noted. Furthermore, an increase in basal glycolysis with a concomitant increase in the cellular maximum glycolytic capacity was also demonstrated in perilesional keloid and FKN fibroblasts (P < 0.05). Mitochondrial function parameters showed increased oxidative phosphorylation in the disease conditions (P < 0.05) indicating functional mitochondria. These findings further suggest that Keloids and FKN demonstrate a switch to a metabolic phenotype of aerobic glycolysis. Increased glycolytic flux inhibition is a potential mechanistic basis for future therapy.
摘要：
瘢痕疙瘩瘢痕和毛囊炎口蹄疫（FKN）是病因不明、治疗不明确的良性纤维增生性真皮病变，通常存在于遗传易感个体中。他们的病理标志包括局部侵袭性侵袭行为加上治疗后的高复发率。鉴于此,我们调查了与正常皮肤和正常扁平非肥厚性瘢痕成纤维细胞作为阴性对照相比,位点特异性瘢痕疙瘩来源的成纤维细胞(内部(中心)和周围(边缘)病变)和FKN的增殖和生物能量细胞特征的关键参数.结果瘢痕疙瘩成纤维细胞增殖和迁移增加，具有统计学意义（P<0.01）和可变的生长动力学。而FKN成纤维细胞显示增殖显著(P<0.001)增加,但与对照相似的迁移曲线。注意到来自疾病状况的成纤维细胞中朝向有氧糖酵解的统计学上显著的代谢转换。此外，在周围瘢痕疙瘩和FKN成纤维细胞中，基础糖酵解增加，细胞最大糖酵解能力同时增加（P<0.05）。线粒体功能参数显示疾病状态下氧化磷酸化增加（P<0.05），表明线粒体有功能。这些发现进一步表明瘢痕疙瘩和FKN表现出转向有氧糖酵解的代谢表型。增加的糖酵解通量抑制是未来治疗的潜在机制基础。
