The relationship between transforming growth factor beta1 expression and cold ischemia injury of rat donor kidney

Cold ischemia injury represents an independent risk factor which favors chronic allograft nephropathy (CAN). In order to investigate the role of transforming growth factor-beta 1( (TGF-beta1) in the progression of CAN, we studied the relationship between the expression of TGF-beta1 and cold ischemia injury in the renal tubular epithelia of rat donor kidney.

A total of 24 Wistar rats were used in this study. In terms of the time of cryopreservation of donor kidney, the 24 Wistar rats were randomly divided into 3 groups: 0 h group(control group), 24 h group, 48 h group. A block removal of donor kidney with in situ perfusion of cooling HC-A preservation solution was adopted. The rat kidney was preserved 0 h, 24h and 48 h at 0-4 degrees C respectively. The morphologic changes of proximal tubular epithelial cells in different cryopreservation time were observed under light microscope and transmission electron microscope. The expression of TGF-beta1 mRNA and protein in proximal tubular epithelial cells of different cryopreservation time group were detected by in situ hybridization and immunohistochemistry analysis.

1. In 24 h group, part of the proximal tubular epithelial cells showed slight degeneration. In 48 h group, the proximal tubular epithelial cells demonstrated severe hydropic degeneration and part of the cells developed necrosis and effluxion. 2. Only a small amount of TGF-beta1 protein and mRNA were expressed in the renal tubular epithelial cells of 0 h group. The positive unit (PU) value of TGF-beta1 protein and mRNA were 6.37+/-2.77 and 5.29+/-2.15, respectively. As the cold ischemia time prolonged, the PU value of TGF-beta1 protein increased at 24 h group (10.20+/-3.27) and 48 h group (17.17+/-3.96) . The PU value of TGF-beta1 mRNA also increased at 24 h group (11.31+/-3.34) and 48 h group (19.01+/-3.53). There was the significant difference of TGF-beta1 protein PU value or mRNA PU value among these groups(P<0.05).

There was the significant correlation between the expression of TGF-beta1 and the degree of cold ischemia injury. The results suggest that TGF-beta1 might play the key role in regeneration and reparation of renal tubular epithelial cell injury. The overexpression of TGF-beta1 might be one of the mechanisms that initiate chronic allograft nephropathy.