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Abstract：
Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co-culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF-β. Additionally, a suspended co-culture multicellular spheroid model revealed molecular-level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro-angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF-β, IL-17, Wnt, Notch, PI3K-Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts-endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.
摘要：
肥厚性瘢痕的形成受成纤维细胞和内皮细胞之间复杂的相互作用的影响。在这项研究中,我们使用体外和体内模型研究了这种关系。临床观察显示病理性瘢痕部位有明显的形态学变化和血管增加。使用OCTA进行进一步分析，免疫组织化学，免疫荧光证实了血管生成参与瘢痕形成。我们的间接共培养系统表明，内皮细胞通过分泌包括VEGF在内的细胞因子来增强成纤维细胞的增殖和迁移。PDGF,bFGF,和TGF-β。此外,悬浮共培养多细胞球体模型揭示了与细胞外基质重塑相关的分子水平变化，细胞行为，炎症反应，和促血管生成活性。此外，KEGG通路分析确定了TGF-β的参与，IL-17,Wnt,缺口,PI3K-Akt,和MAPK通路在调节成纤维细胞活性中的作用。这些发现强调了成纤维细胞-内皮细胞串扰在瘢痕形成中的关键作用，并为治疗干预提供了潜在的靶标。了解这种相互作用的分子机制为开发治疗组织损伤和疾病的创新方法提供了希望。
