INTRAGRAFT TGF-BETA(1) MESSENGER-RNA - A CORRELATE OF INTERSTITIAL FIBROSIS AND CHRONIC ALLOGRAFT NEPHROPATHY

Chronic allograft nephropathy is a relentlessly progressive process an d a major cause of long-term graft dysfunction and ultimate failure. I nterstitial fibrosis, tubular atrophy, and glomerular and vascular les ions characterize this mechanistically unresolved disorder. Given the prominent role of TGF-beta(1) in tissue repair and in fibrosis, we hav e explored the hypothesis that fibrosis and chronic allograft nephropa thy would be distinguished by intragraft TGF-beta(1) mRNA expression. This postulate was tested by mRNA phenotyping of RNA isolated from 127 human renal allograft biopsies. Reverse transcription assisted polyme rase chain reaction was used to amplify and identify ingraft gene expr ession. Our investigation demonstrated a significant correlation betwe en intragraft TGF-beta(1) mRNA display and renal allograft interstitia l fibrosis and chronic allograft nephropathy. In contrast, intragraft expression of mRNA encoding immunoregulatory cytokines, IL-2, IFN-gamm a, IL-4, IL-10, or cytotoxic attack molecules, granzyme B and perforin was not a correlate of interstitial fibrosis or chronic allograft nep hropathy. Our studies identify, for the first time, a significant asso ciation between intragraft TGF-beta(1) mRNA expression and renal allog raft interstitial fibrosis, and advance a candidate molecular mechanis m for chronic allograft nephropathy.