Human mesangial cells secrete a GBM-degrading neutral proteinase and a specific inhibitor.

Human mesangial cells secrete a GBM-degrading neutral proteinase and a specific inhibitor.
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人类肾小球系膜细胞分泌GBM降解中性蛋白酶和特异性抑制剂。

DOI:
10.1038/ki.1989.264
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发表时间:
1989
影响因子:
19.6
通讯作者:
Lovett,DH
Lovett,DH
中科院分区:
医学1区
文献类型:
--
作者:
Martin,J;Davies,M;Thomas,G;Lovett,DH

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人肾小球系膜细胞分泌GBM降解中性蛋白酶和特异性抑制剂。在正常和疾病状态下,控制肾小球细胞外基质(ECM,肾小球基底膜和系膜基质)降解的因素仍然知之甚少。这些结构主要由IV型和V型胶原组成,其对经典间质胶原酶的作用具有高度抗性。在这里,我们报告,一个内在的肾小球细胞类型,人肾小球系膜细胞,分泌:1)一种中性蛋白酶与IV型基底膜胶原蛋白的特异性活性,2)的金属蛋白酶组织抑制剂(TIMP)的特征的抑制蛋白。纯化的酶具有中性的最适pH,由分子量为66和68千道尔顿的碱性(pI 8.4)蛋白质双联体组成,并被钙和锌螯合剂抑制。该酶降解可溶性和基底膜IV型胶原蛋白,但不特异性降解I型或V型胶原蛋白或酪蛋白。培养细胞的免疫组化显示中性蛋白酶抗原的均匀染色,而TIMP抗原在不到三分之一的培养细胞中检测到。这些发现表明,这些蛋白质的合成可能是独立调节的。这些因子的分泌可能在基础或病理条件下肾小球ECM的周转中起重要作用。
Human mesangial cells secrete a GBM-degrading neutral proteinase and a specific inhibitor. The factors operative during normal and disease states which govern the degradation of the glomerular extracellular matrix (ECM, glomerular basement membrane and mesangial matrix) remain poorly understood. These structures consist primarily of types IV and V collagen, which are highly resistant to the action of classical interstitial collagenases. Here we report that an intrinsic glomerular cell type, the human mesangial cell, secretes: 1) a neutral proteinase with specific activity against type IV basement membrane collagen and, 2) an inhibitory protein with the characteristics of the tissue inhibitor of metalloproteinases (TIMP). The purified enzyme has a neutral pH optimum, consists of a basic (pI 8.4) protein doublet with molecular weight of 66 and 68 kilodaltons, and is inhibited by calcium and zinc chelators. The enzyme degrades both soluble and basement membrane type IV collagen, but does not specifically degrade types I or V collagen or casein. Immunohistochemistry of cultured cells demonstrated homogeneous staining for the neutral proteinase antigen, while the TIMP antigen was detected in fewer than one-third of cultured cells. These findings suggest that the synthesis of these proteins may be independently regulated. The secretion of these factors may play an important role in the turnover of the glomerular ECM under basal or pathologic conditions.
DOI: 10.1016/s0021-9258(17)44166-4
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期刊: The Journal of biological chemistry
影响因子: --
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作者:
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DOI: 10.1016/s0174-173x(84)80014-x
发表时间: 1984
期刊: Collagen and related research
影响因子: --
作者:
Mainardi,CL;Hibbs,MS;Hasty,KA;Seyer,JM
通讯作者: Seyer,JM