Nakamura T, Ebihara I, Shirato I, Tomino Y, Koide H
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Am J Pathol. 1991 Aug;139(2):437-50.
The present study was carried out to determine how mRNA levels of extracellular matrix (ECM) components including alpha 1(IV) chain, laminin A, B1 and B2 chains, heparan sulfate proteoglycan (HSPG), alpha 1(I) chain, and alpha 1(III) chain are regulated in the kidney of NZB/W F1 mice. Messenger RNA levels for ECM genes except for laminin A chain increased significantly with the progression of nephritis in NZB/W F1 mice. In the NZW kidneys, however, the mRNA levels for alpha 1(IV) chain, laminin B1 and B2 chains, and HSPG declined markedly with age, whereas those for alpha 1(I) and alpha 1(III) chains showed little difference throughout the experimental period. Messenger RNA levels of beta-actin remained constant, and those of laminin A chain could not be detected in either control or diseased kidneys. Immunofluorescent microscopy showed that the intensity and distribution of staining of collagen IV, laminin, and HSPG in the glomeruli of NZB/W F1 mice increased markedly with the progression of disease. Types I and III collagen were not detected in the glomeruli of NZB/W F1 mice by immunofluorescence until 24 weeks of age, after which increased amounts of these collagens were found in the glomeruli and interstitium with progression of disease. These results suggest that increased levels of mRNA coding for ECM components and increased accumulation of these proteins may contribute to a cascade of events, leading to chronic renal injury in lupus nephritis.
本研究旨在确定包括α1(IV)链、层粘连蛋白A、B1和B2链、硫酸乙酰肝素蛋白聚糖（HSPG）、α1(I)链和α1(III)链在内的细胞外基质（ECM）成分的mRNA水平在NZB/W F1小鼠肾脏中是如何被调控的。在NZB/W F1小鼠中，除层粘连蛋白A链外，ECM基因的mRNA水平随着肾炎的进展而显著增加。然而，在NZW小鼠肾脏中，α1(IV)链、层粘连蛋白B1和B2链以及HSPG的mRNA水平随年龄显著下降，而α1(I)和α1(III)链的mRNA水平在整个实验期间几乎没有差异。β-肌动蛋白的mRNA水平保持恒定，在对照或患病肾脏中均未检测到层粘连蛋白A链的mRNA水平。免疫荧光显微镜检查显示，随着疾病进展，NZB/W F1小鼠肾小球中IV型胶原、层粘连蛋白和HSPG的染色强度和分布显著增加。直到24周龄，通过免疫荧光在NZB/W F1小鼠肾小球中均未检测到I型和III型胶原，此后随着疾病进展，在肾小球和间质中发现这些胶原的量增加。这些结果表明，编码ECM成分的mRNA水平升高以及这些蛋白质的积累增加可能促成一系列事件，导致狼疮性肾炎中的慢性肾损伤。
