肌腱病是以血管过度增生为病理学特征的慢性退行性疾病，其临床治疗效果不佳。既往研究表明炎症修复期血管生成不足或重塑期肌腱内血管生成增多会损害肌腱修复。课题组前期研究发现肌腱病中血管生成过多可能与miR-148a-3p的调控紊乱有关。蛋白芯片、PCR、WB等发现肌腱病中miR-148a-3p的前体pri-miR-148a无差异，而pre-miR148a-3p和miR-148a-3p明显升高，CSTF2T表达增高，CUL4B表达下降，以及 LncRNA NEAT1表达明显升高。基于上述结果我们提出以下假说：CUL4B蛋白调控CSTF2T蛋白泛素化，时序性调控肌腱细胞分泌Tsp-4介导血管生成。本课题拟从分子及细胞水平结合体内和离体实验阐明CUL4B/CSTF2T通过Tsp-4时序性调节血管生成影响肌腱病进程的机制，为肌腱病的治疗提供新靶点。

Tendinopathy is a chronic degenerative disorder pathologically characterized by excessive vascularity with poor therapeutic results. Recent studies have indicated both poor angiogenesis during inflammation and proliferation stage and excessive angiogenesis in tendinopathy during remodeling stage could impair tendon. The mechanism of angiogenesis in tendinopathy remains unclear. Proteomics analysis showed significantly increased expression of CSTF2T (cleavage stimulation factor, 3' pre-RNA, subunit 2, 64kDa, tau variant) and decreased CUL4B (cullin 4B) in tendinopathy samples. At the same time, PCR results have shown expressions of miR-148a-3p, pre-miR-148a-3p were increased abnormally in tendinopathy. Moreover, we found lncRNA NEAT1 expression was also increased in tendinopathy samples. Based on preliminary results, we proposed that CUL4B/CSTF2T axis in tenocytes sequentially regualtes promote angiogenesis of tedinopathy by secretion of Tsp-4. The aim of our research is to provide a theoretical basis for developing a novel therapy in the treatment of tendinopathy.