Glomerular remodelling: novel therapeutic approaches derived from the apparently chaotic growth factor network

Abstract

Glomerular remodelling, i.e. cell and matrix turnover, is a permanent process even in the normal kidney. Within the glomerulus, two cell types, namely the endothelial and mesangial cell, exhibit relatively high turnover and thus high capacity to regenerate following injury, whereas podocytes appear to be in a state of growth arrest with very limited potential for mitosis and apparently even lesser potential for complete cell division. An understanding of how these processes are regulated by growth factors may allow novel therapeutic approaches aimed at deviating the response to injury from the scaring pathway to reconstitution of normal glomerular morphology. Out of the apparently chaotic network of cytokines and growth factors some factors have evolved, which exhibit well-defined actions in the glomerulus that renders them attractive targets for interventions. These include platelet-derived growth factor (PDGF), a central mediator of mesangial cell proliferation and matrix synthesis, vascular endothelial growth factor (VEGF), a central angiogenic mediator regulating endothelial cell proliferation and survival and finally hepatocyte growth factor (HGF), an angiogenic growth factor with additional pronounced activity at the tubulointerstitial level.