Does transforming growth factor b1 play a role in the pathogenesis of chronic allograft rejection?

Abstract

To investigate the potential role of Transforming Growth Factor β1 (TGFβ1) in the pathogenesis of chronic allograft rejection, we studied TGFβ1 expression in a rat aortic allograft model. mRNA and protein expression of total and endogenously active TGFβ1 were analysed in infra-renal orthotopic aortic syngeneic and allogeneic grafts and matched with the histological appearances of the grafts, 2, 4 and 12 weeks post-transplantation. Serum levels of TGFβ1 were also measured. The level of TGFβ1 m RNA and protein expression appeared highest 2 and 4 weeks following transplantation in both syngeneic and allogeneic grafts, with significantly elevated levels of mRNA expression in the 2 week allograft specimens. These time-points correlate histologically with maximal inflammatory cell infiltration of the grafts. By 12 weeks post-transplantation, TGFβ1 mRNA expression is reduced in allogeneic grafts compared to syngeneic grafts. However, detectable levels of total and endogenously active TGFβ1 protein levels in the allografts exceed those measured in the syngeneic grafts at this time point. These results demonstrate the complex expression pattern of this growth factor during the progression of chronic rejection and suggest an aetiological link between TGFβ1 and the process of accelerated graft atherosclerosis.