Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model.
Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model.
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发表时间：
1992-04
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通讯作者：
J. Floege;C. Alpers;M. Burns;P. Pritzl;K. Gordon;W. Couser;Richard J. Johnson
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作者：
J. Floege;C. Alpers;M. Burns;P. Pritzl;K. Gordon;W. Couser;Richard J. Johnson
肾小球系膜细胞外基质（ECM）的扩张和随后的肾小球硬化是大多数进行性肾脏疾病的突出表现。为了研究ECM组分积累的时间顺序，因为它与先前描述的细胞事件有关，在5/6肾切除术后的不同时间从大鼠以及假手术对照组获得活组织检查。活检组织用PAS染色以及PCNA（细胞增殖标记物）、单核细胞/巨噬细胞、I型和IV型胶原、层粘连蛋白、s-层粘连蛋白、纤连蛋白、硫酸乙酰肝素蛋白聚糖和巢蛋白/巢蛋白的免疫染色。从5/6肾切除大鼠获得的活检的免疫染色显示早期肾小球细胞增殖，在第2周达到峰值。在第2周还观察到肾小球簇面积扩张，罕见肾小球显示局灶性硬化。肾小球巨噬细胞流入与后期ECM扩张和肾小球硬化相关。在第2周及以后的时间点，在病理性系膜基质中观察到所有研究的ECM蛋白的进行性积累。在5/6肾切除术后第2周和第6周，对肾小球总RNA的北方分析显示I型胶原mRNA的重新表达以及肾小球IV型胶原mRNA水平的小幅增加（分别是对照RNA的1.2倍和1.4倍）和层粘连蛋白mRNA水平的小幅增加（分别是对照RNA的1.3倍和1.5倍），但s-层粘连蛋白mRNA水平没有增加（分别是对照RNA的1.1倍和0.9倍）。我们的结论是，细胞事件，包括肾小球细胞增殖和巨噬细胞流入与残肾模型中ECM蛋白的基因和蛋白表达增加相关，并可能有助于硬化的发展。
Expansion of the mesangial extracellular matrix (ECM) with subsequent glomerular sclerosis is a prominent finding in most progressive renal diseases. To investigate the chronology of accumulation of ECM components as it relates to previously described cellular events, biopsies were obtained from rats at various times following 5/6-nephrectomy as well as from sham-operated controls. The biopsies were stained with PAS as well as immunostained for PCNA (a cell proliferation marker), monocytes/macrophages, types I and IV collagen, laminin, s-laminin, fibronectin, heparan sulfate proteoglycan and entactin/nidogen. Immunostaining of biopsies obtained from 5/6 nephrectomized rats demonstrated an early glomerular cell proliferation, peaking at week 2. Expansion of the glomerular tuft area with rare glomeruli demonstrating focal sclerosis were also seen at week 2. Glomerular macrophage influx correlated with later ECM expansion and glomerulosclerosis. A progressive accumulation of all ECM proteins investigated was noted in the pathological mesangial matrix at week 2 and later time points. Northern analysis of total glomerular RNA at weeks 2 and 6 after 5/6 nephrectomy showed de novo expression type I collagen mRNA as well as small increases of glomerular mRNA levels for type IV collagen (1.2- and 1.4-fold over control RNA) and laminin (1.3- and 1.5-fold) but not s-laminin (1.1- and 0.9-fold). We conclude that cellular events including glomerular cell proliferation and macrophage influx are associated with increased gene and protein expression by ECM proteins in the remnant kidney model and may contribute to the development of sclerosis.