Expression of TGF-beta 1 and matrix proteins is elevated in rats with chronic rejection.
The pathogenesis of fibrosis in chronic renal allograft rejection remains unknown. Since TGF-beta 1 plays a key role in fibrogenesis, we studied a rat model of chronic allograft rejection that shows similarities to the structural lesion described in patients. We previously demonstrated an increased expression of TGF-beta 1 in human kidney biopsies with acute and chronic rejection. Recipients of renal allografts (F344-Lewis) and isografts (Lewis-Lewis) were sacrificed at 4, 8, 24 and 52 weeks. Characteristic histologic changes of chronic rejection developed in the allografts as early as four weeks and were accompanied by progressive albuminuria significant by eight weeks. Allografts showed a progressive increase in mRNA expression of TGF-beta 1 and matrix proteins during the 52 week course. Increased matrix deposition by immunofluorescence was mostly present in the interstitium and vessels early and in all kidney compartments later. The mRNA expression of plasminogen activator inhibitor, a protease inhibitor stimulated by TGF-beta 1, increased along with TGF-beta 1 and matrix proteins. These results suggest that the fibrosis of chronic renal allograft rejection is mediated, at least partly, by the dual action of TGF-beta 1 on matrix deposition and degradation.
Shihab
F S
FS
Division of Nephrology, University of Utah, Salt Lake City, USA.
Tanner
A M
AM
Shao
Y
Y
Weffer
M I
MI
D000818:Animals; D015152:Blotting, Northern; D002908:Chronic Disease; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D006084:Graft Rejection; D007150:Immunohistochemistry; D016030:Kidney Transplantation; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D014184:Transplantation, Homologous
D016326:Extracellular Matrix Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta