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

Abstract

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. 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. 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. Moreover, SKP1 knockdown inhibited the wnt signaling pathway while inducing ROS production. Collectively, our present study suggests that IBSP promotes the malignant process in hypertrophic scar fibroblasts.