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LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers

A Correction to this article was published on 05 May 2021

This article has been updated


A diabetic foot ulcer (DFU) is one of the most devastating complications of diabetes. It has been reported that lncRNA GAS5 plays a vital role in wound healing in DFUs. However, the specific mechanism remains unclear. In this research, we aimed to investigate the role of GAS5 in wound healing in DFUs as well as the underlying mechanism. qPCR or western blotting was performed to measure the expression levels of GAS5, HIF1A, VEGF and TAF15. CCK-8 or EdU assays, flow cytometry, wound healing assays and tube formation assays were carried out to assess the proliferation, apoptosis, wound healing and in vitro angiogenesis of HUVECs, respectively. RNA pull-down and RIP assays were performed to verify the interaction between GAS5 and TAF15. ChIP and luciferase assays were conducted to verify the binding of TAF15 to the HIF1A promoter. In the DFU mouse model, H&E and Masson staining were used to determine epidermal and dermal thickness and collagen formation. GAS5 and HIF1A were downregulated in the skin tissues of DFU patients, and GAS5 overexpression promoted cell proliferation, wound healing and tubule formation in HG-treated HUVECs. In addition, GAS5 facilitated HIF1A expression by interacting with TAF15. Rescue assays demonstrated that the suppression of HIF1A/VEGF pathway activation partially reversed the functional roles of GAS5 in HUVECs. Furthermore, GAS5 accelerated wound healing by activating the HIF1A/VEGF pathway in mice with DFUs. GAS5 activates the HIF1A/VEGF pathway by binding to TAF15, resulting in accelerated wound healing in DFUs. Our findings may provide a theoretical basis for the clinical treatment of DFUs.

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Fig. 1: GAS5 and HIF1A are downregulated in the skin tissues of DFU patients.
Fig. 2: HG inhibits HUVEC proliferation, wound healing and tubule formation.
Fig. 3: GAS5 overexpression promotes HG-induced HUVEC proliferation, wound healing and tubule formation.
Fig. 4: GAS5 interacts with TAF15 and promotes TAF15 expression.
Fig. 5: GAS5 accelerates HIF1A expression by interacting with TAF15.
Fig. 6: GAS5 promotes cell proliferation, wound healing and tubule formation by activating the HIF1A/VEGF pathway in HG-treated HUVECs.
Fig. 7: GAS5 accelerates DFU wound healing by activating the HIF1A/VEGF pathway.

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All data generated or analyzed during this study are included in this published article.

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This work was supported by General Program of National Natural Science Foundation of China (81870573).

Author information




Guarantor of integrity of the entire study: G-DX. Study concepts and design: G-DX and W-XP. Definition of intellectual content: P-XH and TZ. Literature research: TZ and Y-QZ. Clinical studies: W-XP, TZ, Y-QZ, KP, LX and J-JY. Experimental studies and manuscript editing: W-XP and TZ. Data acquisition: W-XP and Y-QZ. Data analysis: L-JL and KP. Statistical analysis: LX and J-JY. Manuscript preparation: W-XP and P-XH. Manuscript review: P-XH and G-DX.

Corresponding author

Correspondence to Guang-Da Xiang.

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Experiment protocols were approved by the Ethics Committee of Yiyang Central Hospital and experimental procedures were conducted according to the Declaration of Helsinki Principles. The animal experiments involved in this paper were carried out in accordance with the Guidelines for the Care and Use of Laboratory Animals issued by the National Institutes of Health.

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Peng, WX., He, PX., Liu, LJ. et al. LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers. Lab Invest (2021).

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