The relationship between transforming growth factor β1 expression and cold ischemia injury of rat donor kidney

Abstract

Objective 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-β1) in the progression of CAN, we studied the relationship between the expression of TGF-β1 and cold ischemia injury in the renal tubular epithelia of rat donor kidney. Methods 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: 0h group(control group), 24h group, 48h group. A block removal of donor kidney with in situ perfusion of cooling HC-A preservation solution was adopted. The rat kidney was preserved 0h, 24h and 48h at 0-4 °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-β1 mRNA and protein in proximal tubular epithelial cells of different cryopreservation time group were detected by in situ hybridization and immunohistochemistry analysis. Results 1. In 24h group, part of the proximal tubular epithelial cells showed slight degeneration. In 48h 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-β1 protein and mRNA were expressed in the renal tubular epithelial cells of 0h group. The positive unit (PU) value of TGF-β1 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-β1 protein increased at 24h group (10.20 ± 3.27) and 48h group (17.17 ± 3.96) . The PU value of TGF-β1 mRNA also increased at 24h group (11.31 ± 3.34) and 48h group (19.01 ± 3.53). There was the significant difference of TGF-β1 protein PU value or mRNA PU value among these groups(P < 0.05). Conclusion There was the significant correlation between the expression of TGF-β1 and the degree of cold ischemia injury. The results suggest that TGF-β1 might play the key role in regeneration and reparation of renal tubular epithelial cell injury. The overexpression of TGF-β1 might be one of the mechanisms that initiate chronic allograft nephropathy.