MMP2 and MMP9 associate with crescentic glomerulonephritis

Abstract

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiple organ involvement. Lupus nephritis (LN) is a common manifestation with a wide variety of histological appearances. Matrix metalloproteinases (MMP) 2 and 9 are gelatinases capable of degrading glomerular basement membrane type IV collagen, which have been associated with LN. We examine the expression of MMP2 and MMP9 in different classes of LN. Methods: MMP2 and MMP9 expression was detected by immunohistochemistry in sections from renal biopsy specimens with class III, class IV and class V LN (total n = 31), crescentic immunoglobulin A nephropathy (n = 6), pauci-immune glomerulonephritis (n = 7), minimal change disease (n = 2), mesangiocapillary glomerulonephritis (n = 7), diabetic nephropathy (n = 12) and histologically normal controls (n = 8). Results: MMP2 and MMP9 were not expressed in all classes of LN, but were observed in LN with cellular and fibrocellular crescents. MMP2/MMP9 was expressed in cellular and fibrocellular crescents regardless of glomerulonephritis but not observed in inactive fibrous crescents or with mesangial proliferation. This suggests that MMP2 and MMP9 are involved in the development of extracapillary proliferative lesions. Conclusions: MMP2/MMP9 is expressed with active extracapillary proliferation. Further study is necessary to define whether the expression of MMP2/MMP9 reflects a role in glomerular repair after injury, a role in organ-level immune responses or a role as a marker of epithelialization.

Keywords: crescentic glomerulonephritis; glomerulonephritis; immunoglobulin A nephropathy; metalloproteinase; systemic lupus erythematosus.

Fig. 1

(A) (i) MMP2 or MMP9 staining of cellular crescents in patients with LN, (ii) MMP2 or MMP9 staining of fibrocellular crescents in patients with lupus nephritis and (iii) MMP2 or MMP9 staining of fibrous crescents in patients with LN. (B) MMP staining of glomeruli with both fibrous and cellular demonstrating specificity of MMP expression to cellular crescents.

Fig. 2

(i) MMP2 or MMP9 staining of cellular crescents in patients with IgA nephropathy, PIGN, diabetic nephropathy or MCGN. (ii) MMP2 or MMP9 staining of fibrocellular crescents in patients with IgA nephropathy. (iii) MMP2 or MMP9 staining of fibrous crescents in patients with IgA nephropathy, PIGN, diabetic nephropathy or MCGN.