Bergijk E C, Baelde H J, Kootstra C J, De Heer E, Killen P D, Bruijn J A
Department of Pathology, University of Leiden, Netherlands.
J Pathol. 1996 Apr;178(4):462-8. doi: 10.1002/(SICI)1096-9896(199604)178:4<462::AID-PATH501>3.0.CO;2-E.
Increased mRNA and protein expression of extracellular matrix (ECM) components, including fibronectin, occurs during the development of glomerulonephritis and glomerulosclerosis in immunologically mediated kidney diseases. However, in addition to these quantitative changes in ECM expression, qualitative changes in these molecules may contribute to malformations in the composition of the glomerular matrix. These qualitative changes may include alterations in the splicing pattern of the V-region of fibronectin, since this region plays a role in its accumulation. The splicing patterns of this region have been studied in chronic graft-versus-host disease (GvHD) in mice, a model of lupus nephritis, and in chronic serum sickness (CSS) in rats, a model of immune complex nephritis. Cloning of the mouse fibronectin V-region from kidney tissue revealed 96.1 per cent homology with the corresponding domain in rat fibronectin. PCR (polymerase chain reaction) analysis of RNA from isolated glomeruli revealed three isoforms of this region in both mouse and rat fibronectin, namely inclusion or exclusion of the whole region, or exclusion of only the CS1 domain. In both models, increased exclusion of the V-region was observed early in the disease. However, in GvHD the splicing pattern returned to normal, whereas in CSS the shift persisted during the course of the experiment. Differentiated expression of fibronectin isoforms may exert an important effect on the structure and biological function of the glomerulus and may thus play a role in the development of glomerulonephritis and glomerulosclerosis.
在免疫介导的肾脏疾病中，包括纤连蛋白在内的细胞外基质（ECM）成分的mRNA和蛋白质表达在肾小球肾炎和肾小球硬化的发展过程中会增加。然而，除了ECM表达的这些定量变化外，这些分子的定性变化可能导致肾小球基质组成的畸形。这些定性变化可能包括纤连蛋白V区剪接模式的改变，因为该区域在其积累中起作用。已经在小鼠慢性移植物抗宿主病（GvHD）（狼疮性肾炎模型）和大鼠慢性血清病（CSS）（免疫复合物肾炎模型）中研究了该区域的剪接模式。从小鼠肾脏组织中克隆的纤连蛋白V区与大鼠纤连蛋白中的相应结构域具有96.1%的同源性。对分离的肾小球RNA进行的PCR（聚合酶链反应）分析显示，小鼠和大鼠纤连蛋白中该区域有三种异构体，即整个区域的包含或排除，或仅CS1结构域的排除。在两种模型中，疾病早期均观察到V区排除增加。然而，在GvHD中，剪接模式恢复正常，而在CSS中，这种变化在实验过程中持续存在。纤连蛋白异构体的差异表达可能对肾小球的结构和生物学功能产生重要影响，从而可能在肾小球肾炎和肾小球硬化的发展中起作用。
