Circulating levels of matrix metalloproteinases MMP3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy
Circulating levels of matrix metalloproteinases MMP3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy
复制标题
DOI：
10.1093/ndt/15.12.2041
复制
发表时间：
2000-12-01
影响因子：
6.1
通讯作者：
Arias, M
中科院分区：
文献类型：
--
作者：
Rodrigo, E;López-Hoyos, M;Arias, M
背景。慢性移植肾病仍然是移植后一年后移植物损失的主要原因，但功能正常的移植物死亡除外。慢性肾排斥的组织学标志是进行性纤维化，其中细胞外基质转换起重要作用。这种转化是由几个结缔组织蛋白酶系统调节的，基质金属蛋白酶家族就是其中之一。每一种金属蛋白酶对细胞外基质蛋白发挥不同的功能，并可能参与多种疾病的发病机制，如类风湿关节炎和肾小球肾炎。金属蛋白酶在慢性移植肾病的发病机制和肾移植中的作用尚未明确。我们用ELISA法检测了40例慢性移植肾病患者、30例急性排斥反应患者、30例移植肾功能稳定时间相当于慢性移植肾病患者、30例移植肾功能稳定时间相当于急性排斥反应患者和30例健康年龄配对献血者的血清中proMMP-1、proMMP-2和proMMP-3的水平。慢性移植肾病患者血清中proMMP-2和proMMP-3水平明显高于急性排斥反应、移植物功能稳定和健康供者。最引人注目的发现是血清中proMMP-3水平与血清肌酐水平、循环中proMMP-2水平与蛋白尿水平之间的显著正相关。与移植物功能稳定者和健康供者相比，急性排斥反应患者血清中proMMP-1浓度升高。血清proMMP-2和proMMP-3反映慢性移植肾病肾小球和间质细胞外基质的变化，提示其可能在慢性移植肾病的发病机制中发挥作用。急性排斥反应与proMMP-1水平升高有关，这可能是在此过程中产生的许多炎症细胞因子引起的刺激的反映。
Background. Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed.Methods. We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors.Results. Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors.Conclusions. Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.