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.

Vangl2, a planar cell polarity molecule, is implicated in irreversible and reversible kidney glomerular injury

“…Furthermore, in both injury models, Vangl2 mutants had increased ratios of active‐MMP9 to inactive MMP9. MMP9 has previously been shown to be produced by podocytes and altered in a number of glomerular diseases, including lupus nephritis with active, fibrocellular crescents , DN ; viral‐associated glomerulonephritis , membranous and hypertensive nephropathy. MMP9 is also induced by activation of the toll‐like receptor 4 , which mediates the actions of LPS.…”

Identification of MMP9 as a novel key gene in mantle cell lymphoma based on bioinformatic analysis and design of cyclic peptides as MMP9 inhibitors based on molecular docking

“…The expression level of MMP9 can be abnormally elevated in most tumors, and is subject to complex regulation. This could include a very complex regulation process at the level of transcription, mRNA dendritic translocation, and local translation as well as protein activation ( 23 ). Indeed, a high MMP9 level is associated with a poor prognosis in cancer patients ( 25 – 27 ).…”

Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women

“…19,20 Altered MMP2 activity resulting from the presence of specific MMP2 variants was implicated in the destruction of ECM 21 and disruption of basement membrane barriers. 18,22 Insofar as MMP2 is overexpressed in breast cancer, [20][21][22][23] genetic variation in MMP2 gene affecting its expression was shown to contribute to cancer susceptibility. [24][25][26] Few studies evaluated the (likely) link between MMP2 promoter gene variants with altered breast cancer susceptibility and were reported for different populations, but with mixed outcome.…”