Regulation of adhesive interaction between podocytes and glomerular basement membrane

Abstract

Glomerular filtration depends on well-orchestrated cell-cell and cell-matrix contacts of glomerular podocytes. Over the last years critical constituents of these contacts have been identified via molecular approaches. Podocyte cell-matrix interactions have been shown to be mediated in part by alpha(3)beta(1)-integrin heterodimers. Disturbances of integrin matrix interaction lead to detachment of podocytes in vitro, corresponding to the critical event of foot process retraction and glomerular basement membrane (GBM) denudation in vivo. Further, dystroglycan-mediated matrix attachment appears to play a critical role for podocyte foot process architecture. Downstream signaling events are currently elucidated concentrating mainly on integrin-dependent cascades and their consequences for podocyte adhesion and proliferation. An activation of the integrin-linked kinase in podocyte damage in vivo and in vitro makes this molecule a particularly interesting candidate for integrin-mediated inside-out and outside-in signaling in podocytes. Podocyte cell-cell interaction has been characterized in a few studies in vitro, indicating the slit diaphragm to be a modified adherens junction. The structural link between the cell-matrix and cell-cell contacts is maintained by the actin cytoskeleton, which may also enable cross-talk between these two cell contact sites. Examining podocyte function in tissue culture, animal models and human expression studies should allow further detailed dissection of the molecular pathways responsible for maintenance and failure of the glomerular filtration barrier.