Ninth Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Ninth Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Burns. 2022 Feb;48(1):176-183. doi: 10.1016/j.burns.2021.03.003. Epub 2021 Mar 14.
Keloid fibroblasts (KFs) undergo reprogramming of the metabolic phenotype from oxidative phosphorylation to the Warburg effect. However, more studies are needed to demonstrate whether there is a Warburg effect in KFs and to determine whether there is a similar phenomenon in other types of scars or in the proliferative stage of scars. In our study, the mRNA and protein expression of key glycolytic enzymes, glucose consumption and lactate production in KFs, normal skin fibroblasts (NFs), atrophic scar fibroblasts (ASFs), proliferative stage scar fibroblasts (PSSFs), and hypertrophic scar fibroblasts (HSFs) were detected. In addition, the effects of 2-deoxy-d-glucose (2-DG, a glycolysis inhibitor) on cell proliferation in KFs and NFs were studied. We found that the mRNA and protein expression of key glycolytic enzymes in KFs were significantly upregulated compared with those in NFs. Glucose consumption and lactate production in KFs were also higher than that in NFs. However, we found no similar phenomenon in ASFs, PSSFs, or HSFs. When treated with 2mmol/l 2-DG, the cell viability of KFs decreased more than that of NFs. What's more, treatment with increasing concentrations of 2-DG could inhibit cell viability and migration of KFs in a dose-dependent manner. In conclusion, the Warburg effect in KFs is a feature different from ASFs, PSSFs, or HSFs. Keloids are essentially different from other types of scars in terms of energy metabolism. This characteristic of KFs could provide new hope for the early diagnosis and treatment of keloids.
瘢痕疙瘩成纤维细胞（KFs）经历代谢表型的重编程，从氧化磷酸化转变为瓦博格效应。然而，需要更多的研究来证明 KFs 是否存在瓦博格效应，并确定在其他类型的瘢痕或瘢痕增殖期是否存在类似现象。在我们的研究中，检测了 KFs、正常皮肤成纤维细胞（NFs）、萎缩性瘢痕成纤维细胞（ASFs）、增殖期瘢痕成纤维细胞（PSSFs）和肥厚性瘢痕成纤维细胞（HSFs）中关键糖酵解酶的 mRNA 和蛋白表达、葡萄糖消耗和乳酸生成。此外，还研究了 2-脱氧-d-葡萄糖（2-DG，一种糖酵解抑制剂）对 KFs 和 NFs 细胞增殖的影响。我们发现 KFs 中的关键糖酵解酶的 mRNA 和蛋白表达明显上调，与 NFs 相比。KFs 的葡萄糖消耗和乳酸生成也高于 NFs。然而，我们在 ASFs、PSSFs 或 HSFs 中没有发现类似现象。当用 2mmol/L 2-DG 处理时，KFs 的细胞活力比 NFs 下降更多。更重要的是，用递增浓度的 2-DG 处理可呈剂量依赖性地抑制 KFs 的细胞活力和迁移。总之，KFs 中的瓦博格效应是一种不同于 ASFs、PSSFs 或 HSFs 的特征。瘢痕疙瘩在能量代谢方面与其他类型的瘢痕本质上不同。KFs 的这一特征可为瘢痕疙瘩的早期诊断和治疗提供新的希望。
