腹膜透析超滤衰竭(UFF)增加住院率和死亡率，是腹膜透析失败的常见原因。水孔蛋白1（AQP1）是调控水分子的主要通道蛋白，与腹膜透析超滤密切相关。基质金属蛋白酶7（MMP7）是一种基质溶解因子，具有多种生物学功能，但其在腹膜透析中的作用不清。我们发现，MMP7在腹膜间皮细胞及腹透液中均有丰富表达，且腹透液MMP7浓度与腹透超滤呈正相关；应用MMP7刺激腹膜间皮细胞后，AQP1表达显著增加，提示MMP7上调AQP1。研究表明，MAPK磷酸化对AQP1有双向调节作用。我们应用MMP7刺激细胞后，p53磷酸化水平显著升高。因此，我们假设：MMP7通过激活MAPK，上调AQP1，调控腹透超滤。我们将分别上调、下调MMP7明确其对腹膜AQP1的作用及其机制；建立MMP7基因敲除小鼠，验证其通过上调AQP1调控UFF的机制。本研究将深入揭示腹透超滤衰竭的机制，为临床防治UFF提供新靶点。

Ultra-filtration failure (UFF) is a major reason of peritoneal dialysis (PD) failure that caused re-hospitalization and associated with significant mortality. Recent studies have demonstrated that aquaporin-1 (APQ1) is closely related to PD ultra-filtration. .Matrix metalloproteinase 7 (MMP7), also known as matrilysin, is a secreted, zinc- and calcium-dependent endopeptidase that degrades a broad range of extracellular matrix substrates. Its expression is up-regulated in a variety of tumors and in regulating tissue remodeling in many organs, such as liver, lung, and kidney, after chronic injury. MMP7 regulating a diverse array of cellular processes, including extracellular matrix turnover and remodeling, cell proliferation and apoptosis, inflammation, and epithelial-mesenchymal transition. Our previous studies showed that MMP7 was well expressed in peritoneal mesothelial cells, and was significantly up-regulated after high glucose stimulated. Also, in PD patients, MMP7 was closely associated with ultra-filtration. Further studies showed that stimulated with MMP7 could significantly up-regulate AQP1 protein expression. These data suggested that MMP7 up-regulate AQP1 and ultra-filtration. .Studies had shown MAPK could up-regulate AQP1 expression in respiratory system, while down-regulate AQP1 expression in renal. MMP7 was closely associated with MAPK. Our studies also showed that MMP7 could up-regulate p38 phosphorylation in peritoneal mesothelial cells, suggesting that MMP7 might promote AQP1 expression and ultra-filtration via p38 phosphorylation..We are going to validate these hypotheses by the following studies. Firstly, we are going to detect the changes of AQP1 in MMP7 over-expression and knock-down peritoneal mesothelial cells. Secondly, we are going to examine the changes of AQP1 in MMP7 over-expression cells when inhibiting MAPK phosphorylation or MMP7 knock-down cells when activating MAPK. At last, we are going to confirm these changes in MMP7 gene knock-out mice.