TY - JOUR
T1 - Activation of the serine proteinase system in chronic kidney rejection
AU - Tang, Wen Hao
AU - Friess, Helmut
AU - Di Mola, Fabio F.
AU - Schilling, Martin
AU - Maurer, Christoph
AU - Graber, Hans U.
AU - Dervenis, Christos
AU - Zimmermann, Arthur
AU - Büchler, Markus W.
PY - 1998/6/27
Y1 - 1998/6/27
N2 - Background. Activation of the serine proteinase system is an important mechanism that contributes to tissue remodeling. In the present study, we analyzed the expression of urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitor type 1 (PAI-l) in samples of chronically rejected human kid. neys. Methods. Using Northern blot analysis, immunohistochemistry, and a uPA activity assay, specimens from 10 chronically rejected kidneys and 10 normal kidney samples were analyzed. Results. By Northern blot analysis, the expression of uPAR and PAI-1 mRNA was 2.9-fold (P<0.05) and 2.3fold (P<0.05) increased in chronically rejected kidney samples, respectively, compared with normal controls. In contrast, uPA mRNA levels in chronically rejected kidneys were comparable to those in the normal controls. Immunohistochemical analysis in normal kidneys showed weak immunostaining of uPA, moderate to intense uPAR and PAI-1 immunostaining in proximal tubules, and moderate immunostaining in distal tubules, but no signal in the glomeruli or cortical vessels. A similar staining pattern was found in the distal and proximal tubules in rejected kidney tissue sampies. However, in the rejected kidneys, the number of tubules was markedly reduced. In addition, within the glomeruli of rejected kidney samples, there was positive immunostaining for uPA, uPAR, and PAI-1 in the mesangial cells, but negative staining in most of the endothelial cells, whereas the normal kidneys revealed no immunoreactivity in these structures. Conclusion. The demonstrated up-regulation of uPA/ uPAR/PAI-1 in chronic renal rejection is consistent with the plasminogen/plasmin system contributing to tissue remodeling in this disorder. These factors might activate latent transforming growth factor-βs, which have been reported to be enhanced in this disorder, contributing to the generation of the extracellular matrix.
AB - Background. Activation of the serine proteinase system is an important mechanism that contributes to tissue remodeling. In the present study, we analyzed the expression of urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitor type 1 (PAI-l) in samples of chronically rejected human kid. neys. Methods. Using Northern blot analysis, immunohistochemistry, and a uPA activity assay, specimens from 10 chronically rejected kidneys and 10 normal kidney samples were analyzed. Results. By Northern blot analysis, the expression of uPAR and PAI-1 mRNA was 2.9-fold (P<0.05) and 2.3fold (P<0.05) increased in chronically rejected kidney samples, respectively, compared with normal controls. In contrast, uPA mRNA levels in chronically rejected kidneys were comparable to those in the normal controls. Immunohistochemical analysis in normal kidneys showed weak immunostaining of uPA, moderate to intense uPAR and PAI-1 immunostaining in proximal tubules, and moderate immunostaining in distal tubules, but no signal in the glomeruli or cortical vessels. A similar staining pattern was found in the distal and proximal tubules in rejected kidney tissue sampies. However, in the rejected kidneys, the number of tubules was markedly reduced. In addition, within the glomeruli of rejected kidney samples, there was positive immunostaining for uPA, uPAR, and PAI-1 in the mesangial cells, but negative staining in most of the endothelial cells, whereas the normal kidneys revealed no immunoreactivity in these structures. Conclusion. The demonstrated up-regulation of uPA/ uPAR/PAI-1 in chronic renal rejection is consistent with the plasminogen/plasmin system contributing to tissue remodeling in this disorder. These factors might activate latent transforming growth factor-βs, which have been reported to be enhanced in this disorder, contributing to the generation of the extracellular matrix.
UR - http://www.scopus.com/inward/record.url?scp=0032572292&partnerID=8YFLogxK
U2 - 10.1097/00007890-199806270-00015
DO - 10.1097/00007890-199806270-00015
M3 - Article
C2 - 9665081
AN - SCOPUS:0032572292
SN - 0041-1337
VL - 65
SP - 1628
EP - 1634
JO - Transplantation
JF - Transplantation
IS - 12
ER -