Inactive matrix metalloproteinase 2 is a normal constituent of human glomerular basement membrane. An immuno-electron microscopic study.
Remodelling of the extracellular matrix requires tight control not only of matrix synthesis, but also of matrix degradation. Control of matrix degradation is achieved mainly through the matrix metalloproteinase (MMP) enzymes. In the glomerulus, MMP-2 and MMP-9 are believed to be particularly important, as they have activity against type IV collagen. This study has demonstrated by immuno-electron microscopy that most of the immunoreactivity for MMP-2 in the normal glomerulus is located within the glomerular basement membranes and mesangial matrix. mRNA for MMP-2 is also detectable in normal glomeruli, but the other main gelatinase, MMP-9, could not be localized by immuno-electron microscopy. In the normal glomerulus, it seemed likely that MMP-2 is present in an inactive form. To confirm this, in situ zymography was carried out using frozen sections of normal kidney. Baseline activity of normal kidney was relatively weak, but this was dramatically increased by chemical activation of metalloproteinases. The results imply that MMP-2, in an inactive form, is a normal constituent of the extracellular matrix and glomerular basement membranes. Activation would presumably render the matrix 'self-degrading'; membrane-bound MMPs (MT-MMPs) seem particularly likely to be involved in leukocyte penetration of basement membranes in inflammation.
Jalalah
S M
SM
Department of Pathology, King Abdulaziz University, Jeddah, Saudi Arabia.
Furness
P N
PN
Barker
G
G
Thomas
M
M
Hall
L L
LL
Bicknell
G R
GR
Shaw
J A
JA
Pringle
J H
JH
D001485:Basement Membrane / Q000201:enzymology; D005109:Extracellular Matrix / Q000201:enzymology; D015870:Gene Expression; D006801:Humans; D007678:Kidney Glomerulus / Q000201:enzymology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2