RGD Reference Report - Macrophage infiltration and renal damage are independent of matrix metalloproteinase 12 in the obstructed kidney. - Rat Genome Database

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Macrophage infiltration and renal damage are independent of matrix metalloproteinase 12 in the obstructed kidney.

Authors: Abraham, AP  Ma, FY  Mulley, WR  Ozols, E  Nikolic-Paterson, DJ 
Citation: Abraham AP, etal., Nephrology (Carlton). 2012 May;17(4):322-9. doi: 10.1111/j.1440-1797.2012.01567.x.
RGD ID: 7245953
Pubmed: PMID:22257277   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1440-1797.2012.01567.x   (Journal Full-text)

AIM: To determine whether matrix metalloproteinase-12 (MMP-12) plays a functional role in renal interstitial macrophage accumulation, interstitial fibrosis or tubular apoptosis in the unilateral ureteric obstruction (UUO) model. BACKGROUND: MMP-12 is an enzyme that can cleave a number of extracellular matrix proteins and plays a role in macrophage-mediated injury in experimental models of emphysema and antibody-dependent glomerular disease. Macrophages are thought to promote renal fibrosis and tubular damage in the obstructed kidney. Furthermore, upregulation of MMP-12 expression by infiltrating macrophages in the obstructed kidney has been described, but the potential role of MMP-12 in renal injury induced by this non-immune insult is unknown. METHODS: Groups of eight MMP-12 gene deficient (MMP-12(-/-)) and wild type (WT) C57BL/6J mice were killed 3, 7 or 14 days after UUO. RESULTS: Analysis of three different lineage markers found no difference in the degree of interstitial macrophage accumulation between MMP-12(-/-) and WT UUO groups at any time point. Examination of renal fibrosis by total collagen staining, alpha-SMA + myofibroblast accumulation, and TGF-beta1, PAI-1 and collagen IV mRNA levels showed no difference between MMP-12(-/-) and WT UUO groups. Finally, tubular damage (KIM-1 levels) and tubular apoptosis (cleaved caspase-3) in the obstructed kidney was not affected by MMP-12 gene deletion. CONCLUSION: In contrast to lung injury and antibody-dependent glomerular injury, MMP-12 is not required for renal interstitial macrophage accumulation, interstitial fibrosis or tubular damage in the obstructed kidney.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ureteral obstruction  ISOHavcr1 (Mus musculus)7245953; 7245953mRNA:increased expression:kidney tubule:RGD 
ureteral obstruction  IEP 7245953mRNA:increased expression:kidney tubule:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Havcr1  (hepatitis A virus cellular receptor 1)

Genes (Mus musculus)
Havcr1  (hepatitis A virus cellular receptor 1)

Genes (Homo sapiens)
HAVCR1  (hepatitis A virus cellular receptor 1)


Additional Information