β1-integrins and glomerular injury

Abstract

The renal glomerulus is composed of three types of glomerular cells (mesangial cell (MC), endothelial cell and podocyte) and extracellular matrix (ECM) consisting of the glomerular basement membrane (GBM) and mesangial matrix. It constitutes a highly specialized microcirculation in which the permeability characteristics of the capillary wall allow its unique filtration function. The proliferation of MCs, an increase of mesangial ECM and detachment podocyte from GBM are key biological features of progressive glomerulonephritis (GN), leading to glomerular scarring and dysfunction. Thus, the study of the molecular and cellular mechanisms responsible for pathological glomerular alterations may help to elucidate the pathogenesis of progressive glomerular diseases. A growing body of evidence indicates that β1 integrin family (β1 integrins), that mainly mediates cell adhesion to ECM, controls cell behaviors such as cell migration, proliferation, apoptosis and ECM assembly. In addition, a correlation between glomerular expression of β1 integrins and their ligand ECM components is observed in various human and experimental GN, suggesting that altered β1 integrins-mediated cell behaviors may contribute to the progression of GN. It is now becoming apparent that the expression of glomerular β1 integrins is not only critical for maintaining the glomerular capillary permeability but it modulates cell signaling pathways regulating the cell phenotypes involved in the progression of glomerular diseases.