Up-regulation of extracellular matrix proteoglycans and collagen type I in human crescentic glomerulonephritis.
BACKGROUND
The pathogenesis of crescentic glomerulonephritis (CGN) involves cellular migration and proliferation in the urinary space, frequently followed 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 unknown.


METHODS
Renal tissues from 18 patients with CGN were examined immunohistochemically for versican, decorin, biglycan and collagen type I, and were compared with morphologically normal tissues from six tumor nephrectomies. Synthesis of decorin, biglycan, and procollagen type I mRNAs was evaluated by in situ hybridization.


RESULTS
Versican was strongly expressed in cellular crescents and periglomerular areas, whereas decorin and biglycan accumulated in collagen type I-enriched regions, including fibrocellular and fibrous crescents, and interstitial fibrosis. PG and collagen type I accumulation colocalized with myofibroblasts in crescents, periglomerular areas, and interstitium.


CONCLUSIONS
The temporal and spatial patterns of expression demonstrated in this study provide evidence to support pathogenic roles for PG in the evolution of CGN. Based on known biological properties of this molecule, versican may facilitate migration of cells in developing crescents. Decorin and biglycan may contribute to progression of CGN, perhaps via interactions with collagen type I in the remodeled extracellular matrix.
Stokes
M B
MB
Department of Pathology, New York University Medical Center, New York, New York 10016, USA. barry.stokes@med.nyu.edu
Hudkins
K L
KL
Zaharia
V
V
Taneda
S
S
Alpers
C E
CE
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D058575:Decorin; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D037181:Lectins, C-Type; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D053675:Versicans; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; D003094:Collagen; D058575:Decorin; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D053675:Versicans; C546884:BGN protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C546878:DCN protein, human; C508322:VCAN protein, human