New strategy to treat glomerular inflammation by inhibition of mesangial cell matrix metalloproteinases

Therapy of inflammation often requires the attenuation of excess cell proli feration and of extracellular matrix (ECM) accumulation. It is increasingly recognised that matrix metalloprotemases (MMP) play an important role in t he regulation of these two features. For our studies, experimental mesangia l proliferative glomerulonephritis and cultured mesangial cells provided th e inflammation model and the opportunity to evaluate a new therapeutic stra tegy based on MMP inhibition. In vitro Inhibition of MMP activity and synth esis successfully returned the inflammatory mesangial cell phenotype to the normally occurring resting state. In vivo, excess mesangial cell prolifera tion and ECM accumulation in experimental mesangial proliferative glomerulo nephritis were significantly ameliorated by the use of a synthetic MMP inhi bitor. Interestingly, these inhibitors lead to increased mesangial cell apo ptosis. In conclusion, the antiproliferative effect of MMP inhibitors opens new perspectives in the therapy of inflammation, probably even beyond the scope of kidney diseases.