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IBSP mediates fibroblast malignant behaviors in hypertrophic scars via interacting with SKP1

作者:Qin Zhang, Xiaojing Li, Yunlin Ding, Tingting Tao, Teng Quan · 发表于:Burns · 年份:2025 · DOI:10.1016/j.burns.2025.107617 · 被引用次数:3 · 研究领域:Dermatologic Treatments and Research、Connective Tissue Growth Factor Research、Cancer Cells and Metastasis

AIMS: Hypertrophic scars (HS) are fibrotic skin conditions marked by abnormal myofibroblast proliferation and extracellular matrix accumulation. This study aimed to elucidate the functional effects and potential mechanisms of integrin-binding sialoprotein (IBSP) in hypertrophic scar fibroblasts. MATERIALS AND METHODS: IBSP protein and wnt signaling pathway were screened by transcriptomics. To characterize the role of IBSP in hypertrophic scar fibroblasts, CCK8, transwell, and WB experiments were performed. RESULTS: IBSP protein and wnt signaling pathway were screened by transcriptomics. Since IBSP expression was elevated in proliferative scar fibroblasts, we performed IBSP protein knockdown, revealing a significant inhibition of proliferation, migration, and invasion. Western blotting experiments demonstrated that knockdown IBSP could inhibit wnt signaling pathway and collagen formation. Subsequent investigations indicated that IBSP knockdown reduced adenosine triphosphate (ATP) production and heightened reactive oxygen species (ROS) levels in hypertrophic scar fibroblasts. In order to investigate the potential mechanism of IBSP action, mass spectrometry analysis was performed. A combination of mass spectrometry, immunoprecipitation, and immunofluorescence verified that IBSP binds to SKP1. Notably, SKP1 knockdown markedly curtailed malignant behaviors in hypertrophic scar fibroblasts, including proliferation, migration, invasion, collagen synthesis, and ATP production. Moreov...