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

作者：Abraham, Abu P.^*; Ma, Frank Y.; Mulley, William R.; Ozols, Elyce; Nikolic-Paterson, David J.

来源：Nephrology, 2012, 17(4): 322-329.

DOI：10.1111/j.1440-1797.2012.01567.x

• fibrosis
• kidney
• macrophage
• matrix metalloproteinase-12
• tubule

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-beta 1, 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.

• 出版日期2012-5