As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases 
(MMPs), macrophages are well-placed to play an important role in renal fibrosis. 
However, the exact underlying mechanisms and the extent of macrophage 
involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is 
an important contributor to renal fibrosis and MMPs to induction of tubular cell 
EMT. The aim of this study was to investigate the contribution of macrophages 
and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial 
cell line and primary tubular epithelial cells were cultured in activated 
macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated 
J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. 
AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP 
inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by 
monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial 
cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both 
C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced 
tubular cell EMT in C1.1 cells to an extent similar to transforming growth 
factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 
cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence 
that MMPs, specifically MMP-9, secreted by effector macrophages can induce 
tubular cell EMT and thereby contribute to renal fibrosis.