Correlative insights into the immunoexpression of transforming growth factor beta-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-beta) has been recognized as a key mediator of renal fibrogenesis; therefore, the present study was conducted to ascertain immunoexpression of TGF-beta in ARTR. Another purpose of our study was to determine whether TGF-beta could correlate with the interstitial area and to examine a possible relationship between TGF-beta and interstitial alpha-smooth muscle actin (alpha-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-beta-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, alpha-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-beta-1, ET-1, interstitial CD3+ cells, CD68+ cells, alpha-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-beta-1 and ET-1, immunostaining of TGF-beta-1 and alpha-SMA, as well as immunostaining of TGF-beta-1 and interstitial volume. The correlation between immunostaining of TGF-beta-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-beta-1 and interstitial monocytes/macrophages. In controls, all these correlations were not significant. In conclusion, our correlative study suggests a role of TGF-beta-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.
Danilewicz
Marian
M
Department of Nephropathology, Medical University of Łódź, ul. Pomorska 251, 92-213 Łódź, Poland. hobo@csk.am.lodz.pl
Wagrowska-Danilewicz
Małgorzata
M
D000199:Actins / Q000378:metabolism*; D000328:Adult; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D013601:T-Lymphocytes; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014184:Transplantation, Homologous
D000199:Actins; D019332:Endothelin-1; D016212:Transforming Growth Factor beta