4.4 Article

Warburg effect in keloids: A unique feature different from other types of scars

Journal

BURNS
Volume 48, Issue 1, Pages 176-183

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.burns.2021.03.003

Keywords

Keloid; Glycometabolism; Warburg effect; Glycolysis

Funding

  1. National Natural Science Foundation of China [1110318021]

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Keloid fibroblasts (KFs) exhibit a metabolic characteristic known as the Warburg effect, which is distinct from other types of scars or the proliferative stage of scars. KFs show increased expression of key glycolytic enzymes, higher glucose consumption, and lactate production. However, this phenomenon was not observed in atrophic scar fibroblasts (ASFs), proliferative stage scar fibroblasts (PSSFs), or hypertrophic scar fibroblasts (HSFs). Treatment with the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) reduced cell viability in KFs. Keloids have unique energy metabolism compared to other types of scars.
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 2 mmol/l 2-DG, the cell viabilityof 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. (C) 2021 Published by Elsevier Ltd.

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