RGD Reference Report - Macrophage metalloelastase as a major factor for glomerular injury in anti-glomerular basement membrane nephritis. - Rat Genome Database

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Macrophage metalloelastase as a major factor for glomerular injury in anti-glomerular basement membrane nephritis.

Authors: Kaneko, Y  Sakatsume, M  Xie, Y  Kuroda, T  Igashima, M  Narita, I  Gejyo, F 
Citation: Kaneko Y, etal., J Immunol 2003 Mar 15;170(6):3377-85.
RGD ID: 737630
Pubmed: PMID:12626598   (View Abstract at PubMed)

Rat anti-glomerular basement membrane (GBM) nephritis is a model of crescentic glomerulonephritis induced by injection of anti-GBM antiserum. To elucidate the mechanism of glomerular injury, we analyzed the gene expression patterns in the kidneys of anti-GBM nephritis rats using DNA arrays, and found that macrophage metalloelastase/matrix metalloproteinase (MMP)-12 was one of the highly expressed genes in the kidneys on days 3 and 7 after the injection of anti-GBM antiserum. Enhancement of MMP-12 mRNA expression was confirmed by Northern blot analysis, and in situ hybridization revealed that MMP-12 mRNA was expressed in ED-1-positive macrophages and multinuclear giant cells in the glomeruli with crescent. Moreover, these cells were positive with anti-rat rMMP-12 Ab on the section of the kidneys of anti-GBM nephritis rats on day 7. To clarify the role of MMP-12, we conducted a neutralization experiment using anti-rat rMMP-12 Ab, which had an ability to inhibit rMMP-12 activity of degrading natural substrate such as bovine elastin or human fibronectin in vitro. Anti-rat rMMP-12 Ab or control Ig was injected in each of six rats on days 0, 2, 4, and 6 after the injection of anti-GBM antiserum. Consequently, crescent formation and macrophage infiltration in the glomeruli were significantly reduced in the rats treated with anti-rat rMMP-12 Ab, and the amount of urine protein was also decreased. These results disclosed that MMP-12 played an important role in glomerular injury in a crescentic glomerulonephritis model, and inhibition of MMP-12 may lead to a new therapeutic strategy for this disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP12Humancrescentic glomerulonephritis  ISOMmp12 (Rattus norvegicus) RGD 
Mmp12Ratcrescentic glomerulonephritis  IMP  RGD 
Mmp12Mousecrescentic glomerulonephritis  ISOMmp12 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp12  (matrix metallopeptidase 12)

Genes (Mus musculus)
Mmp12  (matrix metallopeptidase 12)

Genes (Homo sapiens)
MMP12  (matrix metallopeptidase 12)


Additional Information