lncRNA UCA1在电针调控肌腱干细胞促进肩袖损伤愈合中的作用及机制研究

肩袖损伤是最常见的肩部疾病，难以愈合，再断率高，严重损伤患者再断率可达90%。电针是促进肩袖损伤愈合的有效方法，但其机制尚不明确。我们前期研究发现电针促进lncRNA UCA1在损伤肩袖肌腱干细胞中高表达，进而抑制干细胞非腱系分化、干细胞凋亡和炎症反应，并可促进干细胞腱系分化、细胞增殖和细胞外基质分泌。同时UCA1与TGF-β1特异性结合，鉴于TGF-β1信号通路在肌腱干细胞中起到中心调控作用，由此推测电针可能通过UCA1/TGF-β1信号通路调控肌腱干细胞促进肩袖肌腱的愈合。本项目拟通过体内外实验，探索电针通过UCA1调控肌腱干细胞分化、增殖、凋亡及细胞外基质分泌的可能机制；以RNA pulldown、RIP及FISH技术，揭示UCA1介导TGF-β1信号通路调控肌腱干细胞生物学特性，促进肩袖损伤愈合的作用机制。研究结果有望以长链非编码RNA和干细胞为视角，为电针治疗肩袖损伤提供新理论。

As the most common shoulder disease, rotator cuff injury is difficult to heal and the re-tear rate of it is high. Electroacupuncture is an effective method to promote the healing of rotator cuff injury, but its mechanism is indeterminate. Our previous researches showed that electroacupuncture promoted the high expression of Long non-coding RNA UCA1 in the tendon stem cells of the injured rotator cuff, and then inhibited the non-tenogenic differentiation of stem cells, apoptosis, and inflammation as well as promoted tenogenic differentiation, proliferation, and extracellular matrix secretion. Furthermore, we also found that UCA1 specially combined with TGF-β1. Considering that the TGF-β1 signaling pathway plays a central role in the regulation of tendon stem cells, it is inferred that electroacupuncture may promote the healing of rotator cuff tendon by regulating the tendon stem cells via the UCA1/TGF-β1 signaling pathway. In this research, we will apply electroacupuncture to explore the mechanism of UCA1 in the regulation of the differentiation, proliferation, apoptosis and extracellular matrix secretion of tendon stem cells in vitro and in vivo. RNA pulldown, RIP and FISH are used to validate the mechanism of TGF-β1 signaling pathway mediated by UCA1 and the biological characteristics of tendon stem cells which could promote the healing of rotator cuff. The results are expected to provide a new theory for electroacupuncture treatment of rotator cuff injury from the view of Long non-coding RNA and stem cells.