Lenz O, Striker L J, Jacot T A, Elliot S J, Killen P D, Striker G E
Renal Cell Biology Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
J Am Soc Nephrol. 1998 Nov;9(11):2040-7. doi: 10.1681/ASN.V9112040.
Mesangial sclerosis is a major feature of progressive renal disease. The mesangium contains mesangial cells and is bounded by the peripheral glomerular basement membrane and endothelial cells. Mesangial cells synthesize and degrade extracellular matrix. Whereas both mesangial and endothelial cells synthesize extracellular matrix components, the degradative pathway, well studied in the former, has not been investigated in endothelial cells. This study examines lines of all three glomerular cell types derived from female B6SJLF1/J mice, as well as mRNA levels for collagens alpha1(I), alpha1(IV), alpha3 (IV), alpha5 (IV), and alpha1 (VI), laminin, tenascin, matrix metalloproteinase-2 (MMP-2), and MMP-9. Type I and IV collagen synthesis was confirmed by enzyme-linked immunosorbent assay. MMP-2 and MMP-9 enzyme activity was measured by zymography. It was found that glomerular endothelial cells are a significant source of collagens, laminin, and tenascin. However, they express only low levels of MMP-2 and no detectable MMP-9. Stimulation with exogenous transforming growth factor-beta1 leads to a significant increase in collagen I, tissue inhibitors of metalloproteinase-1, and MMP-9 in conditioned media. These data suggest that glomerular endothelial cells may play an active role in extracellular matrix remodeling in glomerular disease.
系膜硬化是进行性肾脏疾病的主要特征。系膜包含系膜细胞，由外周肾小球基底膜和内皮细胞界定。系膜细胞合成并降解细胞外基质。虽然系膜细胞和内皮细胞都能合成细胞外基质成分，但前者的降解途径已有深入研究，而内皮细胞的降解途径尚未得到研究。本研究检测了源自雌性B6SJLF1/J小鼠的所有三种肾小球细胞类型系，以及胶原蛋白α1(I)、α1(IV)、α3(IV)、α5(IV)和α1(VI)、层粘连蛋白、腱生蛋白、基质金属蛋白酶-2(MMP-2)和MMP-9的mRNA水平。通过酶联免疫吸附测定法确认了I型和IV型胶原蛋白的合成。通过酶谱法测定MMP-2和MMP-9的酶活性。研究发现，肾小球内皮细胞是胶原蛋白、层粘连蛋白和腱生蛋白的重要来源。然而，它们仅表达低水平的MMP-2，未检测到MMP-9。用外源性转化生长因子-β1刺激可导致条件培养基中胶原蛋白I、金属蛋白酶组织抑制剂-1和MMP-9显著增加。这些数据表明，肾小球内皮细胞可能在肾小球疾病的细胞外基质重塑中发挥积极作用。
