DEGRADATION OF EXTRACELLULAR MATRIX IN HUMAN GLOMERULI

人肾小球细胞外基质的降解

• 批准号: 5202007
• 负责人: L J STRIKER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5202007
• 关键词: basement membrane; cellular pathology; collagen; extracellular matrix; gene expression; glomerulosclerosis; human genetic material tag; human tissue; messenger RNA; metalloendopeptidases; polymerase chain reaction; protein biosynthesis; protein degradation; renal glomerulus; tissue inhibitor of metalloproteinases

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 alpha2 chain of type IV collagen.

肾小球硬化的特征是净积聚 肾小球中的细胞外基质成分并导致其 渐进式消灭。我们开始调查这是否 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。金属蛋白水解酶 降解基底膜的胶原蛋白通过一系列的 抑制物：TIMPs(金属蛋白酶组织抑制物)。我们检查了 TIMPs的mRNAs和相应的多肽是否在 正常肾小球和硬化肾小球。我们利用了非肿瘤部分 在一系列的10名成年患者中，为癌症患者施行了肾切除术。这个 对肾小球进行显微解剖和原位逆转录。 竞争性聚合酶链式反应检测TIMP I和TIMP II MRNAs。两者均在肾小球中检测到，并在 出现肾小球硬化的标本。增加的并不是 由于肾小球内细胞数量的增加 硬化症。这些数据表明，每个细胞的TIMP都是增加的 在与癌症相关的肾小球硬化中的基础。进一步 目前正在进行研究，以确定这一增长是否也 在其他形式的人类肾小球硬化中观察到。我们还有 获得的初步数据表明，编码72kD的mRNA 金属蛋白酶在人肾小球中表达。这个物种出现了 经历与IV型α2链相同的上调 胶原蛋白。