title: Macrophage infiltration and renal damage are independent of matrix metalloproteinase 12 in the obstructed kidney.
abstract: OBJECTIVE
  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, α-SMA + myofibroblast accumulation, and TGF-β1, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology, Monash Medical Centre and Department of Medicine, Monash University, Clayton, Victoria, Australia. abu.abraham@monash.edu
authors.forename: Abu P
authors.initials: AP
authors.lastname: Abraham
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Ma
authors.forename: William R
authors.initials: WR
authors.lastname: Mulley
authors.forename: Elyce
authors.initials: E
authors.lastname: Ozols
authors.forename: David J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement; D004195:Disease Models, Animal; D005355:Fibrosis; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D053508:Matrix Metalloproteinase 12