Macrophage infiltration and renal damage are independent of matrix metalloproteinase 12 in the obstructed kidney
Nephrology, 2012•Wiley Online Library
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 …
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 …
Abstract
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, 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.
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.
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