NDT Advance Access originally published online on January 5, 2007
Nephrology Dialysis Transplantation 2007 22(4):1115-1122; doi:10.1093/ndt/gfl743
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Specific changes in plasma concentrations of matrix metalloproteinase-2 and -9, TIMP-1 and TGF-ß1 in patients with distinct types of primary glomerulonephritis
1INSERM 507, Hôpital Necker, 2CNRS UMR 7131, Hôpital Broussais-HEGP, 3Laboratoire de Biochimie A, Hôpital Necker and 4Département de Néphrologie, Hôpital Necker, Paris, France
Correspondence and offprint requests to: Dr Brigitte Bauvois, CNRS UMR 7131, Hôpital Broussais-HEGP, 102 rue Didot, 75014 Paris, France. Email: brigitte.bauvois{at}brs.aphp.fr
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Abstract |
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Background. Dysregulated renal expression of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMP) and TGF-ß1 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-ß1 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-ß1. In MN patients, decreased MMP-9 level contrasted with a high MMP-2 level and a normal TGF-ß1 level. In the MCNS/FSGS group, increased MMP-2 level contrasted with unchanged MMP-9 and decreased TGF-ß1 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-ß1 levels and the degree of renal dysfunction or with progression toward ESRD.
Conclusions. Plasma concentrations of MMP-2, MMP-9 and TGF-ß1 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.
Keywords: glomerulonephritis; interstitial fibrosis; matrix metalloproteinase; tissue inhibitor of matrix metalloproteinase; transforming growth factor-ß1
Received for publication: 4. 1.06
Accepted in revised form: 15.11.06