细胞外基质（ECM）在肾间质过度沉积是引起间质纤维化的主要原因，缺氧和TGF-β1/Smad2/3信号是推动发展的主要因素。本组发现缺氧下肾小管上皮细胞TGF-β1/Smad2/3信号上调之外，也发现减少ECM生成的TGF-β1/Smad7信号也上调，其激活机制不清；另外发现LncRNA319和SIK1表达上调并存在相关，SIK1是TGF-β1/Smad7信号激活因子，如能提高该信号，能延缓肾纤维化的发展。基于该假说，利用小管上皮细胞和肾穿组织，研究缺氧下LncRNA319通过SIK1激活TGF-β1/Smad7的信号，参与ECM代谢的分子机制。再利用转基因小鼠的肾纤维化模型，靶向干预，原位观察ECM代谢的相关分子的变化。整体了解缺氧下的LncRNA319激活TGF-β1/Smad7信号，调节ECM代谢。以阐明一种LncRNA对ECM代谢调控学说，可能为临床治疗慢性肾脏病提供新的治疗靶点。

Extracellular deposition of extracellular matrix(ECM) in renal interstitial is the main cause of interstitial fibrosis.Hypoxia and TGF-β1/Smad2/3 signaling are the main factors promoting the development.We found that TGF-β1/Smad7 signal is actived in HK-2 cells under hypoxia except TGF-β1/Smad2/3 signal,the TGF-β1/Smad7 signal can inhibits interstitial fibrosis,the activation mechanism is unclear.In addition,we found long noncoding RNA 319 (LncRNA319) and SIK1 are upregulated,and there is a certain relationship between LncRNA319 and SIK1.SIK1 is activator of TGF-β1/Smad7 signal.If the signal can be hightened,the development of renal fibrosis can be delayed.We hypothesized that TGF-β1/smad7 is actived by LncRNA319 through SIK1 under hypoxia to regulate ECM metabolism.To test the hypothesis,we will use tubule epithelial cells line and renal biopsy tissues to investigate the molecular mechanism.The related molecules of ECM metabolism were observed in renal biopsy tissues in situ by the renal fibrosis model of transgenic mice.We can comprehensive understand that TGF-β1/Smad7 signal is actived by LncRNA319 to regulate ECM metabolism under hypoxia.The results will be useful to verify a new mechanism of ECM metabolism,can provide a new therapeutic target for chronic kidney disease.