Role of matrix metalloproteinases in viral-associated glomerulonephritis

Background. Viral infections are a major problem worldwide. Many of these infections are frequently complicated by a virus-associated glomerulonephritis. In glomerulonephritis, progression of renal failure is mainly attributed to the development of extensive glomerular and interstitial fibrosis. Advanced glomerular disease is characterized by the accumulation of extracellular matrix components in the mesangial matrix and glomerular basement membrane. These matrix components are metabolized by matrix metalloproteinases (MMPs) as well as tissue inhibitors of metalloproteinase (TIMPs). Methods. The expression of MMP2, MMP9 and TIMP-1 in human mesangial cells in culture was analysed by RT-PCR. Results. Mesangial cells express the viral receptors toll-like receptor 3 and RIG-I. Activation of these viral receptors by viral RNA exemplified by poly (I:C) RNA leads to a time- and dose-dependent expression of MMP9 without affecting the expression of MMP2 and TIMP-1. To show the specific effect of viral receptors, knockdown experiments with siRNA specific for TLR3 and RIG-I were performed. Conclusion. This novel finding of the functional expression of these viral sensors on glomerular fibrosis may indicate a novel link between viral infections and glomerular inflammation and indicates a pathophysiologic role of viral receptors in these processes.