Intragraft expression of transforming growth factor beta1 gene in isolated glomeruli from human renal transplants.
BACKGROUND
Experimental evidence suggests that transforming growth factor (TGF) beta1 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-beta1.


CONCLUSIONS
TGF-beta1 is a profibrotic influence in human renal transplants. The methods described should prove of benefit in investigating the mechanisms of chronic renal allograft damage.
Nicholson
M L
ML
Department of Surgery, Leicester General Hospital, UK.
Bicknell
G R
GR
Barker
G
G
Doughman
T M
TM
Williams
S T
ST
Furness
P N
PN
D001707:Biopsy, Needle / Q000379:methods; D003094:Collagen / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D007678:Kidney Glomerulus / Q000378:metabolism*; D016030:Kidney Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D018084:Ultrasonography, Interventional
D018076:DNA, Complementary; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen