KGF调控的角质形成细胞外泌体源性LINC01116在增生性瘢痕形成中的作用和机制研究

增生性瘢痕的临床治疗目前仍很复杂和困难, 需要对其形成机制进行更深入的阐明。我们前期研究结果显示增生性瘢痕角质形成细胞外泌体中LINC01116表达上调，并传送到真皮成纤维细胞中发挥促进细胞增殖、迁移及ECM相关促纤维化基因表达的作用；反过来成纤维细胞分泌的重要生长因子KGF能够调控角质形成细胞及其外泌体中LINC01116表达。由此我们提出假设：角质形成细胞外泌体源性LINC01116能通过调控成纤维细胞的生物活性参与增生性瘢痕的形成，从而成为防治增生性瘢痕的新靶标。因此本研究聚焦于探明LINC01116调控人真皮成纤维细胞增殖、迁移和ECM相关促纤维化基因表达的下游机制和KGF调控角质形成细胞中LINC01116表达的上游机制；并进一步体内实验探讨抑制LINC01116表达在裸鼠增生性瘢痕形成中的作用。旨在通过本研究为LINC01116成为增生性瘢痕的临床治疗新靶标提供理论研究基础。

The clinical treatment of hypertrophic scars is still very complicated and difficult at present, and its formation mechanism needs to be further elucidated. Our previous research results showed that LINC01116 was highly expressed in exosomes of hypertrophic scar keratinocytes, and transmitted to dermal fibroblasts through the exosomes, and plays a role in promoting fibroblasts proliferation, migration and expression of ECM-related fibrotic genes. Furthermore, we found that KGF, an important growth factor secreted by fibroblasts, could regulate the expression of LINC01116 in keratinocytes. Therefore, we hypothesize that keratinocytes-derived exosomal LINC01116 can participate in the formation of hypertrophic scars by regulating the biological activity of fibroblasts, thus becoming a new target for the prevention and treatment of hypertrophic scars. Therefore, this study focused on probing the downstream mechanism of LINC01116 regulating human dermal fibroblast proliferation, migration and ECM-related fibrotic gene expression and the upstream mechanism of KGF regulating LINC01116 expression in keratinocytes. Further in vivo experiments will be conducted to investigate the role of inhibition of LINC01116 expression in hypertrophic scar formation in nude mice. This study aims to provide a theoretical basis for LINC01116 to become a new clinical target for the prevention and treatment of hypertrophic scar.