@Article{biocell.2025.066479,
AUTHOR = {Yi Zhang, Hua Jin},
TITLE = {<i>TRIM32</i> Promotes Glycolysis in Keloid Fibroblasts and Progression of Keloid Scars via Regulation of the PI3K/AKT Signaling Pathway},
JOURNAL = {BIOCELL},
VOLUME = {49},
YEAR = {2025},
NUMBER = {8},
PAGES = {1529--1543},
URL = {http://www.techscience.com/biocell/v49n8/63617},
ISSN = {1667-5746},
ABSTRACT = { <b>Objectives:</b> The present study investigated whether Tripartite Motif-Containing Protein 32 (<i>TRIM32</i>) contributes to the aberrant activation of keloid fibroblasts (KFs) via glycolysis. <b>Methods:</b> The expression levels of <i>TRIM32</i>, 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<sup>′</sup>-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. <b>Results:</b> The expression of <i>TRIM32</i> and glycolysis-related proteins was significantly elevated in KFs compared to that in NFs. <i>TRIM32</i> overexpression enhanced the proliferation, invasion, and migration of KFs, as well as extracellular matrix (ECM) deposition, glucose uptake, and ATP production, while <i>TRIM32</i> silencing produced the opposite effects. The glycolysis inhibitor, 2-deoxy-glucose (2-DG), significantly suppressed the biological functions of KFs; however, <i>TRIM32</i> overexpression effectively counteracted the inhibitory effects of 2-DG. <i>TRIM32</i> activated the PI3K/AKT signaling pathway in KFs. The PI3K inhibitor LY294002 decreased cellular glycolysis, with <i>TRIM32</i> overexpression mitigated these inhibitory effects. <b>Conclusion:</b> This study demonstrated that <i>TRIM32</i> 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.},
DOI = {10.32604/biocell.2025.066479}
}