基于转录组学的甲状腺相关眼病眼眶脂肪体积增加关键基因和核心信号通路的研究

Thyroid-associated ophthalmopathy (TAO) is one kind of orbit disease with the highest morbidity. The main pathological changes are the expansion of the orbital adipocytes and fibrosis of the extraocular muscles, which cause feelings of discomfort and decrease of visual acuity. The mechanism of the adipocytes’ expansion is still beyond the scope. Studies demonstrated that genes related to IGF-1, IGF-1R, TSHR and differentiation of adipocyte highly express in orbital adipocytes in TAO. Our group found in last National Natural Science Foundation that CD40-CD40L costimulatory pathway can induce the gene transcription of ICAM-1 in orbital fibroblasts. However the whole genomic research is still lacked. This project intends to explore the mechanism of orbit adipocytes’ expansion by screening the key genes and pathways through high throughput sequencing and prove their roles in the pathogenesis, which maybe helpful for the prevention and therapy for TAO.

甲状腺相关眼病（TAO）是目前发病率最高的眼眶疾病，病理表现为眶内脂肪体积增加和眼外肌纤维化，严重影响患者容貌外观和身心健康。目前眶内脂肪体积增加的具体机制尚不明确。国内外研究发现，胰岛素样生长因子（IGF-1）及其受体（IGF-1R）相关基因、促甲状腺激素受体（TSHR）与脂肪化相关基因等均证实在TAO患者脂肪细胞中高表达，本课题组在既往的研究中发现CD40-CD40L共刺激通路可以启动细胞间粘附分子（ICAM-1）基因表达，但是完整的基因组学研究尚欠缺，本课题拟利用高通量测序RNA-seq技术检测眼眶脂肪细胞的转录组信息，进一步研究关键基因和核心转导通路，并分析验证其在TAO的发病过程中的机制和作用。本研究有望为临床TAO脂肪增生的防治提供新的方向。

甲状腺相关眼病（thyroid-associated ophthalmopathy, TAO）是目前发病率最高的眼眶疾病，病理表现为眶内脂肪体积增加和眼外肌纤维化，目前眶内脂肪体积增加的具体机制尚不明确。本课题在上一个国家自然科学基金项目中完善了CD40-CD40L共刺激通路对于TAO发病机制中的炎症反应阶段的作用，但完整的基因组学研究尚欠缺。本课题中，我们根据既定计划完成了TAO患者和对照组样本的收集和分析，通过对眼眶脂肪组织的高通量测序，发现了甲状腺相关眼病和正常人之间的差异表达基因，发现其参与的生物学过程及细胞内信号通路与甲状腺相关眼病临床表现基本相符。后续相关差异基因的验证也证实了测序结果的真实可靠性。根据构建的GO-tree和Path-Act-Net，课题组拟选出后续甲状腺相关眼病发病机制基础研究的靶点，基本完成了课题的研究内容。