Specific changes in plasma concentrations of matrix metalloproteinase-2 and -9, TIMP-1 and TGF-beta1 in patients with distinct types of primary glomerulonephritis.
BACKGROUND
Dysregulated renal expression of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMP) and TGF-beta1 contribute to the development of tubulo-interstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). There is little information on the circulating levels of these proteins in human GNs. Here, we assessed whether different histopathological GN types could be associated with distinct plasma patterns of MMPs and regulatory proteins.


METHODS
Protein levels of MMP-2, MMP-9, TGF-beta1 and TIMP-1 were measured by ELISA in plasma from venous blood of 108 untreated patients with various types of primary GN defined by kidney biopsy, namely IgAN (n=63), membranous GN (MN, n=26), minimal change nephrotic syndrome (MCNS, n=12) and focal and segmental glomerular sclerosis (FSGS, n=7), and were compared with levels in 50 healthy subjects. Plasma samples were assayed for gelatinolytic activity (zymography).


RESULTS
Zymography detected the proforms of MMP-2 and MMP-9. Compared with controls, IgAN patients exhibited a significant, parallel decrease in plasma levels of MMP-2, MMP-9 and TGF-beta1. In MN patients, decreased MMP-9 level contrasted with a high MMP-2 level and a normal TGF-beta1 level. In the MCNS/FSGS group, increased MMP-2 level contrasted with unchanged MMP-9 and decreased TGF-beta1 levels. Plasma concentration of TIMP-1 was elevated in all GN groups. There was no correlation between baseline MMP-2/MMP-9/TIMP-1/TGF-beta1 levels and the degree of renal dysfunction or with progression toward ESRD.


CONCLUSIONS
Plasma concentrations of MMP-2, MMP-9 and TGF-beta1 significantly differed between the various histopathological types of primary GNs, thus suggesting the involvement of different underlying mechanisms in the regulation of glomerular and tubulointerstitial fibrosis in these renal diseases.
Bauvois
Brigitte
B
INSERM 507, CNRS UMR 7131, Hôpital Necker, Paris, France. brigitte.bauvois@brs.aphp.fr
Mothu
Nadya
N
Nguyen
Juliette
J
Nguyen-Khoa
Thao
T
Nöel
Laure-Hélène
LH
Jungers
Paul
P
D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000097:blood* / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9