Expression of decorin, biglycan, and collagen type I in human renal fibrosing disease.
BACKGROUND
The extracellular matrix proteoglycans decorin and biglycan may have a pathogenic role in renal fibrosing disease via regulation of the activity of growth factors, such as transforming growth factor-beta, and effects on collagen type I fibrillogenesis. The expression of decorin and biglycan in human glomerular diseases characterized by mesangial sclerosis is unknown.


METHODS
Decorin, biglycan, and collagen type I were localized immunohistochemically in human renal biopsy cases of amyloidosis (N = 18), diabetic nephropathy (N = 11), fibrillary glomerulonephritis (N = 5), immunotactoid glomerulopathy (N = 5), light-chain deposition disease (N = 4), idiopathic mesangial sclerosis (N = 4), and nephrosclerosis (N = 6), and in morphologically normal tissues obtained from tumor nephrectomies (N = 8). Decorin and biglycan mRNA synthesis was evaluated by in situ hybridization.


RESULTS
Decorin and biglycan protein were not identified in normal glomeruli. Decorin accumulated in amyloid deposits, but not in deposits of fibrillary glomerulonephritis or immunotactoid glomerulopathy. Biglycan weakly accumulated in amyloid deposits, and both decorin and biglycan weakly stained mesangial nodules in cases of morphologically advanced light-chain deposition disease and diabetic nephropathy. In all analyzed cases, irrespective of the underlying disease, decorin and biglycan accumulated in glomeruli in areas of fibrous organization of the urinary space and in areas of tubulointerstitial fibrosis. Biglycan, but not decorin, accumulated in the neointima of arteriosclerotic blood vessels. Decorin and biglycan mRNA synthesis was detected at sites of proteoglycan accumulation in glomeruli, interstitium, and neointima. Collagen type I colocalized with decorin and biglycan deposits.


CONCLUSIONS
Differences in extracellular matrix proteoglycan composition may be diagnostically useful in distinguishing morphologically similar diseases. Distinct patterns of proteoglycan expression may be related to modulation of specific growth factor activity in different glomerular diseases.
Stokes
M B
MB
Department of Pathology, University of Washington Medical Center, Seattle, WA 98195-6100, USA.
Holler
S
S
Cui
Y
Y
Hudkins
K L
KL
Eitner
F
F
Fogo
A
A
Alpers
C E
CE
D000686:Amyloidosis / Q000473:pathology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology; D058578:Biglycan; D001706:Biopsy; D003094:Collagen / Q000032:analysis / Q000235:genetics*; D058575:Decorin; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics; D005920:Glomerular Mesangium / Q000737:chemistry / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology*; D009395:Nephritis, Interstitial / Q000473:pathology / Q000503:physiopathology; D009400:Nephrosclerosis / Q000473:pathology / Q000503:physiopathology; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
C546884:BGN protein, human; D058578:Biglycan; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D003094:Collagen