肌成纤维细胞（Myofibroblast，MFB）在口腔黏膜下纤维性变（Oral submu cous fibrosis，OSF）致病机制中的地位日益凸显。预实验中我们发现OSF中存在以CXCR3为受体的趋化因子网络，同时在槟榔碱刺激下MFB的TGF-β1表达与其迁移能力成剂量依赖关系，但机制不明。趋化因子受体硫酸化是细胞迁移研究的热点，而TPST-1是催化其硫酸化的关键酶，受膜蛋白调控。为解释预实验结果，本项目提出 “在OSF中TGF-β1通过激发膜蛋白EGFR自分泌信号，增强TPST-1催化活性，进而调控CXCR3酪氨酸残基硫酸化，最终控制MFB迁移”的科学假设。针对假设，本课题结合体内、体外实验，探讨TGF-β1通过调控CXCR3硫酸化促使MFB迁移的具体分子机制，并在大样本OSF临床标本中探讨硫酸化关键分子的诊断价值，为阐释OSF结缔组织纤维化机理提供新的实验依据。

Myofibroblast (MFB) is one key for the pathopoiesis of oral submucous fibrosis (OSF). We found that chemokine receptor 3 (C-X-C chemokine receptor 3，CXCR3) was expressed in OSF. Meanwhile, there was a dose-dependent relationship between TGF-β1 expression and the migration potential of MFB when MFB was simulated by arecoline. These results suggested that TGF-β1 might improve the migration of MFB by the CXCR3. However, few reseach was focued on this field. In recent years, tyrosine sulfation of CXCR3 has been the hot topic of the cell migration, and TPST-1 was one of the important catalytic enzymes for tyrosine sulfation. So, we concluded that in OSF pathopoiesis, TGF-β1 can regulate the transcription of EGFR, then improve the TPST-1 activity, which could control the tyrosine sulfation of CXCR3 and the migration of MFB. By combining with in vivo and in vitro experiments, we wish to find the regulating way of MFB migration induced by TGF-β1, which can provide new molecular foundation for OSF pathopoiesis.