Intragraft expression of transforming growth factor β1 gene in isolated glomeruli from human renal transplants

Background: Experimental evidence suggests that transforming growth factor (TGF) beta 1 is a fibrogenic cytokine. The histopathological changes of chronic renal allograft nephropathy are dominated by fibrotic changes and TGF-beta may have an important aetiological role. This study investigated the relationship between intragraft TGF-beta gene expression and extracellular matrix protein deposition in human renal allografts. Methods: Sixteen cadaveric renal transplant recipients immunosuppressed with cyclosporin and steroids were studied. Individual glomeruli were isolated from protocol needle-core biopsies and, following messenger RNA extraction, intragraft gene expression was studied by reverse transcriptase-polymerase chain reaction. Collagen III deposition in these renal transplant biopsies was examined by immunohistochemistry and quantified by computerized histomorphometry. Results: There was a positive correlation between renal cortical collagen III immunostaining and the levels of glomerular complementary DNA for TGF-beta 1. Conclusion: TGF-beta 1 is a profibrotic influence in human renal transplants. The methods described should prove of benefit in investigating the mechanisms of chronic renal allograft damage.