Correlative insights into the immunoexpression of transforming growth factor β-1 in acutely rejected renal allografts

Recent data suggest that early changes in the process of acute renal transplant rejection (ARTR) occurring during the first 3 months after transplantation include interstitial fibrosis. Transforming growth factor beta (TGF-β) has been recognized as a key mediator of renal fibrogenesis; therefore, the present study was conducted to ascertain immunoexpression of TGF-β in ARTR. Another purpose of our study was to determine whether TGF-β could correlate with the interstitial area and to examine a possible relationship between TGF-β and interstitial α-smooth muscle actin (α-SMA), endothelin-1 (ET-1) expression, interstitial T lymphocytes, and monocytes/macrophages.Twenty-four renal allograft biopsy specimens obtained from patients with ARTR were examined using percutaneous renal biopsy. As a control, we used 11 allograft biopsy specimens obtained from patients without any sign of rejection. Staining intensities of TGF-β-1 in tubuli and of ET-1 in the endothelium of peritubular capillaries, in arterioles, and in the renal tubular epithelial cells were recorded semiquantitatively, whereas interstitial CD3+ cells, CD68+ cells, α-SMA expression, and the interstitial area were assessed quantitatively using computer image analysis system.Our study revealed that in the ARTR group, the mean values of the immunoexpression of TGF-β-1, ET-1, interstitial CD3+ cells, CD68+ cells, α-SMA expression, and the interstitial area were significantly increased as compared with controls. In the ARTR group, there were significant positive correlations between immunostaining of TGF-β-1 and ET-1, immunostaining of TGF-β-1 and α-SMA, as well as immunostaining of TGF-β-1 and interstitial volume. The correlation between immunostaining of TGF-β-1 and CD 3+ cells tended to be negative; however, this did not reach statistical significance. We did not find any significant relationship between TGF-β-1 and interstitial monocytes/macrophages. In controls, all these correlations were not significant.In conclusion, our correlative study suggests a role of TGF-β-1 in early interstitial fibrotic changes in acutely rejected renal allografts, and we hypothesize that endothelin-1 and myofibroblasts pathways may play an important role in this process.