Expression of transforming growth factor-beta isoforms in human glomerular diseases.
Protein and mRNA expression of TGF-beta isoforms, TGF-beta 1, -beta 2 and -beta 3, and deposition of fibronectin containing extra domain A (fibronectin EDA+) and plasminogen activator inhibitor-1 (PAI-1) were studied in human chronic glomerulonephritis and diabetic nephropathy. Normal kidneys showed similar, weak immunostaining for all three TGF-beta isoforms. TGF-beta mRNA expression was weak for all isoforms with TGF-beta 1 > TGF-beta 3 >> TGF-beta 2. In thin basement membrane disease and minimal change disease, disorders where extracellular matrix accumulation is not a feature, immunoreactivity and mRNA expression did not differ from normal. In contrast, diseases characterized by extracellular matrix accumulation (IgA nephropathy, focal and segmental glomerulosclerosis, crescentic glomerulonephritis, lupus nephritis and diabetic nephropathy) all showed significantly increased expression of the three TGF-beta isoforms in glomeruli and the tubulointerstitium. While glomerular and tubulointerstitial deposition of two matrix components induced by TGF-beta, fibronectin EDA+ and PAI-1, was significantly elevated in all diseases with matrix accumulation, correlation analysis revealed a close relationship primarily with TGF-beta 1. We conclude that, for a spectrum of human glomerular disorders, increased protein expression of all three TGF-beta isoforms and proteins induced by TGF-beta is associated with pathological accumulation of extracellular matrix.
Yamamoto
T
T
Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, USA.
Noble
N A
NA
Cohen
A H
AH
Nast
C C
CC
Hishida
A
A
Gold
L I
LI
Border
W A
WA
D000918:Antibody Specificity; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000032:analysis; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007536:Isomerism; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta