Differential expression of collagen type IV alpha-chains in the tubulointerstitial compartment in experimental chronic serum sickness nephritis
✍ Scribed by Van Vliet, Anita I.; Van Alderwegen, Isolde E.; Baelde, Hans J.; de Heer, Emile; Killen, Paul D.; Kalluri, Raghu K.; Bruijn, Jan Anthonie; Bergijk, Eline C.
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 698 KB
- Volume
- 189
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
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 4(IV) collagen early during disease development, followed by an increase in 1(IV) through 3(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 1(IV), 2(IV), and 4(IV). Statistical correlations were found between the mRNA levels of 1(IV) and 2(IV) collagen and between 3(IV) and 4(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 1(IV) and 3(IV) collagen, and between 1(IV) and 4(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 1(IV) and 2(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.