Decreased collagen-degrading activity could be a marker of prolonged mesangial matrix expansion.
BACKGROUND
Mesangial matrix expansion is caused by the overproduction and/or the impaired proteolytic degradation of the extracellular matrix. However, the relative contribution of these changes to the development of prolonged mesangial matrix expansion is still poorly understood. We aimed to elucidate the relative role of the matrix metalloproteinase (MMP)/tissue inhibitors of metalloproteinases (TIMPs) system in the development of prolonged mesangial matrix expansion.


METHODS
We prepared two rat models, showing reversible or prolonged mesangial matrix expansion, induced by a single injection or two consecutive injections of anti-Thy-1.1 monoclonal antibody 1-22-3, respectively. We analyzed the glomerular expression of type I and type IV collagens; MMP-2, -9, and -13; membrane type 1-MMP (MT1-MMP); TIMP-1; and urinary type I collagen-degrading activity in both models.


RESULTS
There were no differences in glomerular mRNA levels of type I and type IV collagens between the reversible and the prolonged models. MMP-9 mRNA expression and protein level was lower in the prolonged model than in the reversible one, whereas there were no differences in mRNA levels of MMP-2, -13, MT1-MMP, or TIMP-1 between the two models. Urinary type I collagen-degrading activity in the prolonged model was lower than that in the reversible one. Furthermore, there was a significant correlation between the mesangial matrix expansion and urinary type I collagen-degrading activity.


CONCLUSIONS
Impaired expression of MMP-9 may contribute to the development of prolonged mesangial matrix expansion. Analysis of urinary type I collagen-degrading activity may provide additional diagnostic information in mesangial proliferative glomerulonephritis. Mesangial matrix expansion is caused by the overproduction and/or the impaired proteolytic degradation of the extracellular matrix. However, the relative contribution of these changes to the development of prolonged mesangial matrix expansion is still poorly understood. We aimed to elucidate the relative role of the matrix metalloproteinase (MMP)/tissue inhibitors of metalloproteinases (TIMPs) system in the development of prolonged mesangial matrix expansion.
Tomita
Masayuki
M
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, 951-8510, Niigata, Japan.
Koike
Hiroko
H
Han
Gi Dong
GD
Shimizu
Fujio
F
Kawachi
Hiroshi
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000652:urine; D003199:Computer Systems; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000378:metabolism*; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000378:metabolism* / Q000652:urine; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000276:immunology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D024042:Collagen Type I; D024141:Collagen Type IV; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D017364:Collagenases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C417249:collagenase 1; D020780:Matrix Metalloproteinase 9