P53介导TGF-β1/mTOR信号通路调控翼状胬肉成纤维细胞增殖和转分化中的作用研究

翼状胬肉是一种常见的慢性增殖性疾病，具有类似肿瘤样特性，目前发病机制仍不清。手术是治疗本病的主要手段，但仍有2%~39%的复发率。进一步研究翼状胬肉的发病机制具有重要的理论和临床意义。翼状胬肉成纤维细胞增殖和转分化是此病发生的主要病理改变，但其信号通路目前尚不清。已报道p53在翼状胬肉组织中的高表达，p53是一种抑癌基因，可以诱导细胞凋亡与抑制肿瘤生长。在前期的实验中已证实mTOR信号通路可促进翼状胬肉成纤维细胞增殖和转分化。结合p53和mTOR是调节器官纤维化的重要信号通道，本课题组在已有的工作基础上，提出了“P53介导TGF-β1/mTOR信号通路调控翼状胬肉成纤维细胞增殖和转分化”的假说。本文拟通过体内外实验、在不同的作用环节进行干预研究p53和TGFβ1/mTOR的关系，为翼状胬肉的发病机制提供新的线索和可能的分子机制。

Pterygium is a common chronic disease with the character of tumor. The mechanism of pterygium is still unclearly. The principal treatment for pterygium is surgical removal, but the rate of recurrence is 2% ~ 39%. More insights into the pathogenesis of pterygium are required. Fibrovascular proliferation plays a privital role in pterygium pathogenesis. It is reported that p53 shows higher expression in pterygium. P53 is a tumor suppressor gene, which can induce apoptosis and inhibit tumor growth. It has been confirmed in previous experiments that mTOR signaling pathway can promote the proliferation and transdifferentiation of pterygium fibroblasts. Combined with p53 and TGF-β1/mTOR, it is an important signal channel to regulate organ fibrosis. Based on the previous work, our team proposed the hypothesis that p53 mediates TGF-β1/mTOR signal pathway to regulate the proliferation and transdifferentiation of pterygium fibroblasts. In order to provide new clues and possible molecular mechanism for the pathogenesis of pterygium, the relationship between p53 and mTOR was studied through experiments in vitro and in vivo.