DEGRADATION OF EXTRACELLULAR MATRIX IN HUMAN GLOMERULI

肾小球硬化症的特征是 细胞外基质成分在肾小球和结果， 进行性闭塞我们开始调查 这种情况可能是由于合成和合成之间的不平衡造成的。 细胞外基质的降解。金属蛋白酶， 降解的基底膜胶原蛋白被一系列 抑制剂：TIMP（金属蛋白酶组织抑制剂）。我们研究 是否TIMPs mRNA和相应的肽表达， 正常肾小球和硬化肾小球。我们利用了非肿瘤的部分， 在一系列10名成人患者中进行的癌症肾切除术。的 将肾小球显微解剖并原位逆转录。 竞争性聚合酶链反应检测TIMP I和II mRNA。两者都在肾小球中检测到，并在肾小球中增加。 存在肾小球硬化的标本。涨幅不 由于肾小球中细胞数量的增加， 硬化症这些数据表明，TIMP在每个细胞上增加， 肾小球硬化与癌的关系。进一步 研究正在进行中，以确定这种增加是否也 在其他形式的人类肾小球硬化中观察到。我们还 获得的初步数据表明，编码72 kd的mRNA 金属蛋白酶在人肾小球中表达。这个物种似乎 经历与IV型α-2链相同的上调 胶原

Glomerulosclerosis is characterized by a net accumulation of extracellular matrix components in the glomerulus and results in its progressive obliteration. We started to investigate whether this condition could result from an imbalance between synthesis and degradation of the extracellular matrix. The metalloproteinases which degrade basement membrane collagens are inactivated by a series of inhibitors: TIMPs (tissue inhibitors of metalloproteinases). We examined whether TIMPs mRNAs and the corresponding peptide were expressed in normal and sclerotic glomeruli. We utilized the non tumoral part of nephrectomies performed for cancer in a series of 10 adult patients. The glomeruli were microdissected and reverse-transcribed in situ. Competitive polymerase chain reaction was performed for TIMP I and II mRNAs. Both were detected in the glomeruli and were increased in the specimens in which glomerulosclerosis was present. The increase was not due to an increase in the number of cells in the glomeruli with sclerosis. These data suggest that TIMPs are increased on a per cell basis in the glomerulosclerosis associated with carcinoma. Further studies are in progress to determine whether this increase is also observed in other forms of human glomerulosclerosis. We have also obtained preliminary data indicating that mRNA coding for the 72kd metalloproteinase is expressed in human glomeruli. This species appears to undergo the same upregulation than the alpha-2 chain of type IV collagen.