Transforming growth factor beta-induced connective tissue growth factor and chronic allograft rejection.
Late loss of allograft function is primarily attributed to chronic rejection (CR). There are no effective treatments for CR and the underlying cause of the disease is unknown. This study compared events that occurred within cardiac allografts placed in mice that received either anti-CD4 therapy and develop CR or anti-CD40L therapy and do not develop CR. Both TGFbeta and connective tissue growth factor (CTGF), which is induced by TGFbeta, were expressed in grafts with CR but were not expressed in grafts without CR. TGFbeta transfection of allografts in anti-CD40L-treated recipients resulted in CTGF expression and CR. However, TGFbeta transfection of syngeneic grafts did not result in CTGF expression or CR. These data indicate that TGFbeta alone is insufficient to induce CR and that CTGF is required. Further, antigenic stimulation is required for TGFbeta induction of CTGF. Thus, CTGF may serve as a therapeutic target for CR.
Csencsits
K
K
Section of General Surgery, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Wood
S C
SC
Lu
G
G
Faust
S M
SM
Brigstock
D
D
Eichwald
E J
EJ
Orosz
C G
CG
Bishop
D K
DK
D000818:Animals; D023201:CD40 Ligand / Q000276:immunology; D055513:Connective Tissue Growth Factor; D005260:Female; D006084:Graft Rejection / Q000473:pathology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D023201:CD40 Ligand