MMP-9 contributes to glomerulosclerosis by causing profibrotic changes in podocytes and glomerular endothelial cells

Abstract Background Glomerulosclerosis is characterized by progressive (myo)fibroblast accumulation and collagen deposition involving profibrotic changes of podocytes and endothelial cells. A profibrotic role of MMP-9 in interstitial fibrosis has been reported. Whether MMP-9 plays a role in glomerulosclerosis is not clear yet. Methods A mouse glomerulosclerosis model [adriamycin nephropathy (AN)] was produced in MMP-9-/- and wild-type control BALB/c mice. All animals were sacrificed at 4 weeks after injection. Albuminuria (albumin to creatinine ratio) and calculated GFR were measured. Gomori Trichrome (GT) and Sirius Red (SR) staining were used for assessment of glomerular fibrosis. Profibrotic changes of podocytes or glomerular endothelial cells were examined by confocal microscopy using immunofluorescence staining (IF) of desmin or α-SMA with P-cadherin or VE-cadherin. Results Albuminuria was reduced while GFR was increased in MMP-9-/- AN mice compared with those of wild-type mice. Confocal microscopy showed a significant decrease in podocytes double-stained with P-cadherin and desmin and decrease in glomerular endothelial cell co-staining with VE-cadherin and α-SMA, demonstrating that MMP9-/- AN mice were protected from profibrotic changes in podocytes and glomerular endothelial cells. Glomerulosclerosis was significantly reduced in MMP-9-/- AN mice compared to that of WT, as demonstrated by GT and SR staining. Conclusions MMP-9 contributes to profibrotic changes in podocytes and glomerular endothelial cells and thereby glomerulosclerosis.