Li Qi, Qin Zelian, Nie Fangfei, Bi Hongsen, Zhao Runlei, Pan Bailin, Ma Jianxun, Xie Xiang
Department of Plastic and Reconstructive Surgery, Peking University Third Hospital, Beijing, 100191, China.
Department of Plastic and Reconstructive Surgery, Peking University Third Hospital, Beijing, 100191, China.
Biochem Biophys Res Commun. 2018 Feb 5;496(2):641-647. doi: 10.1016/j.bbrc.2018.01.068. Epub 2018 Jan 11.
Keloids, tumor-like fibroproliferative cutaneous lesions, were reported in metabolic disturbance. However, the metabolic character remains unclear. The purpose of this study is to determine if glycolytic reprogramming is important for the pathogenesis of keloids and to assess the inhibition potential of glycolysis in keloid treatment. An intracellular metabolic profile assay was used to compare metabolic phenotypes between normal skin fibroblasts and keloid fibroblasts (NFs and KFs). Our data indicated that KFs underwent reprogramming of their metabolic phonotype from oxidative phosphorylation to aerobic glycolysis (Warburg effect) with augmented glycolysis and glycolytic capacity. Both gene and protein assays showed that the expression of glycolytic enzymes was upregulated in KFs compared to NFs. Our data showed higher glucose influx and lactate production in KFs compared to NFs. Furthermore, the proliferation of KFs was suppressed in a dose-dependent and time-dependent manner after inhibition of glycolysis with 2-deoxy-glucose (2-DG). Taken together, these findings suggested that keloids underwent a reprogrammed metabolic phenotype of aerobic glycolysis. This was essential for keloid hyperplasia, and glycolytic inhibitors might provide a potential treatment for keloids.
瘢痕疙瘩是一种肿瘤样的纤维增生性皮肤病变，在代谢紊乱中已有报道。然而，其代谢特征仍不清楚。本研究的目的是确定糖酵解重编程对瘢痕疙瘩发病机制是否重要，并评估糖酵解抑制在瘢痕疙瘩治疗中的潜力。采用细胞内代谢谱分析方法比较正常皮肤成纤维细胞和瘢痕疙瘩成纤维细胞（NFs和KFs）之间的代谢表型。我们的数据表明，KFs经历了代谢表型从氧化磷酸化到有氧糖酵解（瓦氏效应）的重编程，糖酵解和糖酵解能力增强。基因和蛋白质检测均显示，与NFs相比，KFs中糖酵解酶的表达上调。我们的数据显示，与NFs相比，KFs中的葡萄糖摄取和乳酸生成更高。此外，用2-脱氧葡萄糖（2-DG）抑制糖酵解后，KFs的增殖以剂量依赖性和时间依赖性方式受到抑制。综上所述，这些发现表明瘢痕疙瘩经历了有氧糖酵解的重编程代谢表型。这对瘢痕疙瘩增生至关重要，糖酵解抑制剂可能为瘢痕疙瘩提供一种潜在的治疗方法。
