Highly expressed VGLL3 in keloid fibroblasts promotes glycolysis and collagen production via the activation of Wnt/β-catenin signaling

Purpose

This study investigated the effects and related mechanisms of Vestigial-like family member 3 (VGLL3) on keloid fibroblast (KF) proliferation, apoptosis, collagen production, and glycolysis.

Methods

Western blot, qRT-PCR, and immunohistochemistry were used for determining VGLL3 expression. KF viability, proliferation, and apoptosis were assessed using CCK-8 assay, EdU assay, and flow cytometry. Changes in the protein expression levels of α-SMA, fibronectin, collagen I, and collagen III were examined utilizing western blotting. The pathways related to VGLL3 were analyzed using Gene Set Enrichment Analysis. Changes in glycolysis were assessed by measuring oxygen consumption rate (OCR), extracellular acidification rate (ECAR), glucose uptake, and lactate production. WNT2 and β-catenin protein levels were measured using western blotting.

Results

VGLL3 was upregulated in human keloid tissues. In KFs, overexpression of VGLL3 inhibited cell apoptosis, promoted cell proliferation and protein expression of α-SMA, fibronectin, collagen I, and collagen III. Moreover, it reduced OCR level, and increased the levels of ECAR, glucose uptake, and lactate production. On the other hand, the knockdown of VGLL3 had the opposite effect. WNT2 and β-catenin protein levels were enhanced by overexpression of VGLL3 and reduced by VGLL3 knockdown. Silencing of WNT2 reversed the effects of VGLL3 on apoptosis, proliferation, collagen production, and glycolysis in KFs.

Conclusions

VGLL3 promoted glycolysis in KFs and keloid progression, which was achieved through the activation of Wnt signaling pathway. Therefore, targeting VGLL3 may be a promising therapeutic strategy for the treatment of keloids.