Intragraft TGF-beta 1 mRNA: a correlate of interstitial fibrosis and chronic allograft nephropathy.
Chronic allograft nephropathy is a relentlessly progressive process and a major cause of long-term graft dysfunction and ultimate failure. Interstitial fibrosis, tubular atrophy, and glomerular and vascular lesions characterize this mechanistically unresolved disorder. Given the prominent role of TGF-beta 1 in tissue repair and in fibrosis, we have explored the hypothesis that fibrosis and chronic allograft nephropathy 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 polymerase chain reaction was used to amplify and identify ingraft gene expression. Our investigation demonstrated a significant correlation between intragraft TGF-beta 1 mRNA display and renal allograft interstitial fibrosis and chronic allograft nephropathy. In contrast, intragraft expression of mRNA encoding immunoregulatory cytokines, IL-2, IFN-gamma, IL-4, IL-10, or cytotoxic attack molecules, granzyme B and perforin was not a correlate of interstitial fibrosis or chronic allograft nephropathy. Our studies identify, for the first time, a significant association between intragraft TGF-beta 1 mRNA expression and renal allograft interstitial fibrosis, and advance a candidate molecular mechanism for chronic allograft nephropathy.
Sharma
V K
VK
Rogosin Institute, Department of Transplantation Medicine and Extracorporeal Therapy, New York Hospital-Cornell Medical Center, New York, USA.
Bologa
R M
RM
Xu
G P
GP
Li
B
B
Mouradian
J
J
Wang
J
J
Serur
D
D
Rao
V
V
Suthanthiran
M
M
D001483:Base Sequence; D001706:Biopsy; D002908:Chronic Disease; D017931:DNA Primers / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology / Q000502:physiology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology; D014184:Transplantation, Homologous
D017931:DNA Primers; D007376:Interleukin-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases