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 s tudied in human chronic glomerulonephritis and diabetic nephropathy. N ormal kidneys showed similar, weak immunostaining for all three TGF-be ta isoforms. TGF-beta mRNA expression was weak for all isoforms with T GF-beta 1 > TGF-beta 3 much greater than TGF-beta 2. In thin basement membrane disease and minimal change disease, disorders where extracell ular matrix accumulation is not a feature, immunoreactivity and mRNA e xpression did not differ from normal. In contrast, diseases characteri zed by extracellular matrix accumulation (IgA nephropathy, focal and s egmental glomerulosclerosis, crescentic glomerulonephritis, lupus neph ritis and diabetic nephropathy) all showed significantly increased exp ression of the three TGF-beta isoforms in glomeruli and the tubulointe rstitium. While glomerular and tubulointerstitial deposition of two ma trix components induced by TGF-beta, fibronectin EDA+ and PAI-1, was s ignificantly elevated in all diseases with matrix accumulation, correl ation analysis revealed a close relationship primarily with TGF-beta 1 . We conclude that, for a spectrum of human glomerular disorders, incr eased protein expression of all three TGF-beta isoforms and proteins i nduced by TGF-beta is associated with pathological accumulation of ext racellular matrix.