Open Access

ARTICLE

TRIM32 Promotes Glycolysis in Keloid Fibroblasts and Progression of Keloid Scars via Regulation of the PI3K/AKT Signaling Pathway

Yi Zhang¹, Hua Jin^2,*

1 Department of Burn, Yixing People’s Hospital, Yixing, 214200, China
2 Department of Dermatology and Venereal Disease, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310023, China

* Corresponding Author: Hua Jin. Email:

BIOCELL 2025, 49(8), 1529-1543. https://doi.org/10.32604/biocell.2025.066479

Received 09 April 2025; Accepted 04 August 2025; Issue published 29 August 2025

Abstract

Objectives: The present study investigated whether Tripartite Motif-Containing Protein 32 (TRIM32) contributes to the aberrant activation of keloid fibroblasts (KFs) via glycolysis. Methods: The expression levels of TRIM32, pyruvate dehydrogenase kinase 1 (PDK1), hexokinase 2 (HK2), and glucose transporter 1 (GLUT1) in normal human skin fibroblasts (NFs) and KFs were analyzed using RT-qPCR analyses and western blotting. Cellular proliferation, invasion, and migration were evaluated using Transwell, wound healing, 5-ethynyl-2^′-deoxyuridine (EdU), and cell counting kit-8 (CCK-8) assays. The extracellular acidification rate (ECAR) was measured using the XF96 Extracellular Flux Analyzer. Glucose uptake and ATP production were measured using specific assay kits. The expression of α-smooth muscle actin (α-SMA) was determined by immunofluorescence assays. The expression levels of collagen I, α-smooth muscle actin (α-SMA), fibronectin (FN), and components of the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway were quantified by western blotting. Results: The expression of TRIM32 and glycolysis-related proteins was significantly elevated in KFs compared to that in NFs. TRIM32 overexpression enhanced the proliferation, invasion, and migration of KFs, as well as extracellular matrix (ECM) deposition, glucose uptake, and ATP production, while TRIM32 silencing produced the opposite effects. The glycolysis inhibitor, 2-deoxy-glucose (2-DG), significantly suppressed the biological functions of KFs; however, TRIM32 overexpression effectively counteracted the inhibitory effects of 2-DG. TRIM32 activated the PI3K/AKT signaling pathway in KFs. The PI3K inhibitor LY294002 decreased cellular glycolysis, with TRIM32 overexpression mitigated these inhibitory effects. Conclusion: This study demonstrated that TRIM32 enhances the viability of KFs by regulating glycolytic activity, potentially mediated via the PI3K/AKT signaling pathway, thereby suggesting novel therapeutic approaches for the treatment of keloids.

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Keywords

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Supplementary Material

Supplementary Material File

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