Up-regulation of extracellular matrix proteoglycans and collagen type I inhuman crescentic glomerulonephritis

Background. The pathogenesis of crescentic glomerulonephritis (CGN) involve s cellular migration and proliferation in the urinary space, frequently fol lowed by fibrous organization. Extracellular matrix proteoglycans (PGs) may regulate these events via effects on cellular migration, interactions with growth factors, including transforming growth factor-beta (TGF-beta), and control of collagen fibrillogenesis. The expression of PG in human CGN is u nknown. Methods. Renal tissues from 18 patients with CGN were examined immunohistoc hemically for versican, decorin, biglycan and collagen type I, and were com pared with morphologically normal tissues from six tumor nephrectomies. Syn thesis of decorin, biglycan, and procollagen type I mRNAs was evaluated by in situ hybridization. Results. Versican was strongly expressed in cellular crescents and periglom erular areas, whereas decorin and biglycan accumulated in collagen type I-e nriched regions, including fibrocellular and fibrous crescents, and interst itial fibrosis. PG and collagen type I accumulation colocalized with myofib roblasts in crescents, periglomerular areas, and interstitium. Conclusions. The temporal and spatial patterns of expression demonstrated i n this study provide evidence to support pathogenic roles for PG in the evo lution of CGN. Based on known biological properties of this molecule, versi can may facilitate migration of cells in developing crescents. Decorin and biglycan may contribute to progression of CGN, perhaps via interactions wit h collagen type I in the remodeled extracellular matrix.