长链非编码RNA Snhg8在慢性肾脏病导致的蛋白质能量消耗中的作用

Chronic kidney disease (CKD) is a serious public health problem and its incidence is increasing year by year all around the world. Protein-energy wasting (PEW) is a major complication of CKD and usually increases mortality rate. The clinical manifestation of PEW is skeletal muscle wasting and its pathogenesis is unclear. Our preliminary study has shown that long non-coding RNA (lncRNA) involved in the development of skeletal muscle wasting. And lncRNA Snhg8 was increased in the muscle of CKD mice significantly. Inhibition of Snhg8 in vitro reduced the expression of muscle RING-finger protein-1 (MuRF1) and blocked the combination of NF-κB and MuRF1 promoter region caused by serum of CKD mice. We plan to investigate the mechanism by which lncRNA Snhg8 leads to muscle wasting. Specifically, we will validate if CKD stimulates lncRNA Snhg8 expression and if this response increases MuRF1 transcription induced by NF-κB and hence enhancing muscle proteolysis. The aim of this proposal is to identify a new mechanism leading to skeletal muscle wasting during CKD. We believe the results of this project will provide new ideas for prevention and treatment of skeletal muscle wasting occurring in CKD patients.

慢性肾脏病（chronic kidney disease, CKD）是一个显著的公共健康问题，发病率逐年上升。蛋白质能量消耗（protein-energy wasting, PEW）是CKD的主要并发症之一，导致CKD患者的死亡率增加。PEW临床表现为骨骼肌萎缩，发病机制尚不明确。我们前期研究发现多条长链非编码RNA（lncRNA）参与小鼠骨骼肌萎缩的发生发展。其中，lncRNA Snhg8在CKD小鼠骨骼肌中上升尤为显著。体外敲抑Snhg8降低了肌环指蛋白1（MuRF1）的表达，且抑制了CKD小鼠血清引起的转录因子NF-κB与MuRF1启动子的结合。本项目拟探索lncRNA Snhg8介导CKD骨骼肌萎缩的新作用，提出CKD刺激骨骼肌lncRNA Snhg8表达，通过NF-κB促进MuRF1转录，增强蛋白质降解，终致骨骼肌萎缩。本项目有望为临床防治CKD所致骨骼肌萎缩提供新思路。

慢性肾脏病(chronic kidney disease,CKD)是一个显著的公共健康问题，约50%的CKD患者合并蛋白质能量消耗(protein-energy wasting,PEW)，临床表现为骨骼肌萎缩。长链非编码RNA(long non-coding RNA,lncRNA)参与骨骼肌萎缩的发生发展。我们的研究发现了lncRNA Snhg8介导CKD骨骼肌萎缩的新机制。LncRNA Snhg8在CKD小鼠骨骼肌中表达显著增加，并通过NF-κB增强肌环指蛋白1(MuRF1)的转录表达，增强蛋白质降解，终致骨骼肌萎缩。在小鼠骨骼肌特异性敲除Snhg8则可延缓CKD所致的骨骼肌萎缩，为防治CKD-PEW提供新思路。