Modulation of matrix gelatinases and metalloproteinase-activating process in acute kidney rejection.
Changes in matrix metalloproteinase (MMP) activities would contribute to the accumulation of extracellular matrix during acute kidney allograft rejection. MMP-2 and MMP-9 and other gelatinolytic activities were examined in the rejected graft and the urine of a rat model of acute kidney rejection (orthotopic allotransplantation from a Buffalo donor to a Wistar-Furth recipient) by either zymography or fluorescence assay. MMP-2, membrane type 1 (MT1)-MMP, and tissue inhibitor of metalloproteinase (TIMP)-2 were also examined by immunodetection. The proMMP-2 activity and protein level increased in the graft during rejection when compared with normal Buffalo kidney, whereas activated MMP-2 decreased. TIMP-2 protein levels were markedly decreased and MT1-MMP proteolytic fragments (44-40 kDa) were undetectable. This suggests an altered MT1-MMP-dependent processing of proMMP-2 into active MMP-2 due to a diminished TIMP-2 level in acute kidney rejection. In the urine the overall gelatinolytic activity decreased considerably, although activity associated with an as yet unidentified 78-kDa protein appeared 6 days after transplantation.
Laboratory of Molecular Medicine, UQAM-Sainte-Justine Hospital, C.P. 8888, Succursale Centre-Ville Montreal, Quebec, H3C 3P8, Canada.
Alain
A
Laplante
Dingyi
D
Liu
Michel
M
Demeule
Borhane
B
Annabi
Gerard F
GF
Murphy
Pierre
P
Daloze
Huifang
H
Chen
Richard
R
Béliveau
D000818:Animals; D018093:Gelatinases / Q000378:metabolism*; D006084:Graft Rejection / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology; D007678:Kidney Glomerulus / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D016030:Kidney Transplantation / Q000473:pathology*; D007700:Kinetics; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051381:Rats; D011915:Rats, Inbred BUF; D011920:Rats, Inbred WF; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014184:Transplantation, Homologous
D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1