Differential expression of collagen IV isoforms in experimental glomerulosclerosis

✍ Scribed by Bergijk, Eline C.; Van Alderwegen, Isolde E.; Baelde, Hans J.; De Heer, Emile; Funabiki, Kazuhiko; Miyai, Hironobu; Killen, Paul D.; Kalluri, Raghuram K.; Bruijn, Jan Anthonie

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 402 KB
• Volume: 184
• Category: Article
• ISSN: 0022-3417
• DOI: 10.1002/(sici)1096-9896(199803)184:3<307::aid-path5>3.0.co;2-w

✦ Synopsis

Expansion of the glomerular mesangial matrix (MM), thickening of the glomerular basement membrane (GBM), and eventually the development of glomerulosclerosis are often seen in immunologically mediated kidney diseases. In addition to quantitative changes in the extracellular matrix (ECM), qualitative changes in ECM molecules may contribute to alterations in the composition of the glomerular matrix. The expression of collagen IV, 1-5(IV) mRNA, and polypeptides was therefore investigated during the development of chronic graft-versus-host disease (GvHD) in mice, a model for lupus nephritis, and in chronic serum sickness (CSS) in rats, a model for membranous nephropathy. Immunohistochemical studies showed increased mesangial expression of 1 and 2 early in the disease, but only late in the GBM. In contrast, 3 and 4 increased in the GBM during disease, but not in the MM. The mRNA levels for all collagen IV chains were increased in isolated glomeruli before morphological alterations were detectable. The mRNA increase was earlier and more profound for 3, 4 and 5 than for 1 and 2. Expression of 3(IV) was greatest in GvHD, whereas expression of 4 was greatest in CSS. As determined by in situ hybridization (ISH), 1 mRNA was observed dispersed in the glomerulus, but 3, 4, and 5 mRNAs were mainly located in cells at the periphery of the glomerular tuft. The changes in the relative abundance of collagen IV mRNA in disease states may perturb the collagen IV network, altering glomerular structure and function, and may thereby play a central role in the development of glomerulonephritis and glomerulosclerosis. 1998