Increased steady-state levels of mRNA coding for extracellular matrix components in kidneys of NZB/W F1 mice

Abstract

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.