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Fibronectin (FN) is an extracellular matrix component which appears in different isoforms, due to alternative mRNA splicing of the ED-A, ED-B, and IIICS regions, and subsequent post-translational modifications. The FN isoforms, some of which occur specifically during fetal development and in fibrogenic diseases, have been reported to play a role in various biological functions, such as regulation of the matrix assembly, adhesion, and proliferation. The contribution of these FN isoforms to the pathogenesis of chronic renal diseases, which are also fibrogenic disorders, is not well known. This study therefore examined the distribution of FN isoforms in renal diseases by immunohistochemistry, with a panel of isoform-specific monoclonal antibodies (MAbs), applied to 63 abnormal renal biopsies and ten normal controls. Normal kidneys contained total FN (MAb IST4) both in the mesangial and in the interstitial extracellular matrix (ECM), but only traces of ED-A-positive FN (MAb IST9), and no ED-B-positive FN (MAb BC1) or oncofetal FN (MAb FDC6) was found in normal renal tissue. All patients with renal disease demonstrated increased total FN staining of the interstitium and the mesangium. Periglomerular fibrotic lesions and fibrous crescents showed massive accumulation of total FN, whereas the amount of total FN in the ECM of obsolescent glomeruli was decreased, compared with that in normal mesangial ECM. Oncofetal (FDC6), EDB-negative (MAb IST6), ED-A-positive, and ED-B-positive FN isoforms were found in glomerular ECM accumulations and in fibrous crescents. Tubulointerstitial fibrotic lesions predominantly contained the ED-A-positive FN isoform, whereas in globally sclerotic glomeruli, predominantly ED-B-positive FN was observed. The expression of FN isoforms was similar in all renal diseases studied. These results show that in various renal diseases, oncofetal (FDC6) FN and ED-A- and ED-B-positive isoforms of FN accumulate at locations of chronic lesions, independently of the aetiology of the disease. The deposition of these isoforms in human renal tissue may play a role in the modulation of the immune response by attracting monocytes and lymphocytes to the injured kidney. Furthermore, because the ED-B-positive FN isoform is highly susceptible to proteolytic degradation, its accumulation may play a role in scar formation and tissue repair. ED-B-positive FN forms a temporary scaffold supporting the cells, which can easily be cleared by proteolytic degradation once new tissue has been produced at the site of injury. Copyright © 2000 John Wiley & Sons, Ltd.

The expression of collagen type IV chains in the renal tubulointerstitium was investigated during the development of chronic serum sickness (CSS) in rats, a model for immune complex-mediated renal disease. Immunohistochemical studies showed increased expression of α4(IV) collagen early during disease development, followed by an increase in α1(IV) through α3(IV) collagen subchain expression, especially in the tubular basement membrane. Dot-blot and in situ hybridization analysis showed a transient increase in steady-state mRNA levels for all collagen IV subchains during the development of CSS, which was most abundant for α1(IV), α2(IV), and α4(IV). Statistical correlations were found between the mRNA levels of α1(IV) and α2(IV) collagen and between α3(IV) and α4(IV), in line with the results of others which showed that these chains are co-distributed as heterotrimer collagen type IV molecules. However, additional correlations were found between the mRNA levels coding for α1(IV) and α3(IV) collagen, and between α1(IV) and α4(IV) mRNAs in the course of CSS. These abnormal correlations support the hypothesis that changes occur in the co-expression of the collagen IV subchains during the development of CSS. In addition, a strong correlation was found between the presence in the tubulointerstitium of α1(IV) and α2(IV) collagen chains, on the one hand, and the tubulointerstitial influx of R73+ and ED1+ cells, on the other, suggesting the involvement of inflammatory cells in the observed alterations in matrix production. Changes in the relative abundance of collagen IV chains in disease states may perturb the collagen IV network in the tubulointerstitial compartment and thereby play a role in the development of renal failure. Copyright © 1999 John Wiley & Sons, Ltd.