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，随着病程的发展缺氧成为推动发展的主要因素。本组发现缺氧下肾小管上皮细胞(HK-2)的Caveolin-1（Cav-1）介导的内吞增强，影响MMP-2在细胞膜上的活化，使MMP-2活性下降，而胞内MMP-2的前体表达增加，其确切机制不清。另外证实Cav-1与MMP-2活化存在一定的相关，如能探讨Cav-1与MMP-2互作，了解MMP-2活性下降机制，能延缓肾纤维化的发展。因此提出假说缺氧下Cav-1通过CSD与MMP-2互作，阻止MMP-2前体活化，导致MMP-2活性下降从而影响ECM代谢平衡。基于该假说，利用HK-2细胞和肾穿组织，再利用小鼠的肾纤维化模型，原位观察ECM代谢的相关分子的变化。整体了解缺氧下的Cav-1与MMP-2互作，调控ECM代谢。以阐明一种新的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 are the main factors promoting the development.We found that endocytosis induced by Caveolin-1(Cav-1) is enhanced in HK-2 cells under hypoxia,affects the activation of MMP-2 in the cell membrane, so MMP-2 activity decreased, while the intracellular pro-MMP-2 expression increased, the exact mechanism is unclear. In addition, we confirmed there is a certain correlation between the change of Cav-1 and MMP-2 activation. If Cav-1 and MMP-2 can be explored, it may be helpful to understanding the mechanism of MMP-2 activity reduction and delay the development of renal fibrosis. Therefore,we hypothesized that Cav-1 interacts with MMP-2 through CSD under hypoxia to prevent the activation of pro-MMP-2,leading to the decrease of MMP-2 activity and affecting the balance of ECM metabolism.To test the hypothesis,we will use tubule epithelial cells line ,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 mice.We can comprehensive understand that Cav-1 interacts with MMP-2 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.