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Inhibiting Warburg Effect Can Suppress the Biological Activity and Secretion Function of Keloid Fibroblasts

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  • Basic Science/Experimental
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Abstract

Background

Keloids have always been a difficult problem in the clinic. In our previous study, we demonstrated a Warburg effect in keloid fibroblasts (KFs), like tumors. In this study, we aimed to investigate the effects of the suppression of the Warburg effect on the biological activity and function of KFs.

Methods

KFs were isolated and cultured with different concentrations of oxamate, a classical competitive lactate dehydrogenase A (LDHA) inhibitor. First, the suppression effect of oxamate on the Warburg effect in KFs was verified. After treatment with oxamate, a scratch wound assay, real-time PCR, flow cytometry, CCK8 kit, and western blotting were used to detect the migration ability, collagen production, apoptosis, cell proliferation, cell cycle distribution, and related molecular mechanisms in KFs.

Results

As expected, oxamate inhibited the Warburg effect in KFs in a dose-dependent manner. After the inhibition of the Warburg effect in KFs, the cell migration rate decreased significantly, the mRNA transcription levels of type I collagen and α-SMA were significantly lower, the cell apoptosis rate increased significantly, the cell proliferation activity decreased significantly, and G0/G1 phase cells in KFs increased significantly. The expression of cyclin D1 and its upstream regulatory factors, Akt protein and GSK3 β (phospho S9), decreased significantly.

Conclusion

Inhibiting the Warburg effect in KFs significantly suppressed cell proliferation, enhanced cell apoptosis, inhibited cell migration ability, reduced collagen secretion, and induced G0/G1 arrest through the Akt-GSK3β-Cyclin D1 pathway. Therefore, inhibiting the Warburg effect in KFs may provide a new option for the prevention and treatment of keloids.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 8180081563).

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Authors and Affiliations

  1. Ninth Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Zhiguo Su, Jincai Fan, Liqiang Liu, Hu Jiao, Jia Tian, Cheng Gan, Zengjie Yang & Rong Huang

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  1. Zhiguo Su
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  2. Jincai Fan
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  3. Liqiang Liu
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Correspondence to Hu Jiao.

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Su, Z., Fan, J., Liu, L. et al. Inhibiting Warburg Effect Can Suppress the Biological Activity and Secretion Function of Keloid Fibroblasts. Aesth Plast Surg 46, 1964–1972 (2022). https://doi.org/10.1007/s00266-022-02899-3

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  • DOI: https://doi.org/10.1007/s00266-022-02899-3

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