4 - Glomerular Cell Biology and Podocytopathies

Abstract

Four distinct cell types constitute the renal glomerulus as a functional and integrated syncytium to ascertain glomerular filtration. Podocytes and glomerular endothelial cells comprise the glomerular filtration barrier. Together, both cells allow for a size and charge selective glomerular filtration due to their specialized three-dimensional structure, extensive glycocalyx coating and due to synthesis of the unique glomerular basement membrane. Mesangial cells regulate glomerular filtration by means of contraction, release of vasoactive substances and maintain the health of glomerular endothelial cells. Parietal epithelial cells build the Bowman's capsule to prevent leakage of the primary urine to the tubulointerstitium, can contribute to glomerular scarring and are thought to constitute a potential regenerative reservoir for podocytes in development, maturation and eventually in adulthood. An intricate glomerular cellular crosstalk is the prerequisite for normal glomerular development and health. Thus, primary injury of one glomerular cell type can affect all other glomerular cell types. Most forms of glomerular injury result from immunologic mechanisms, which enclose humoral and cellular immune responses. There appear to be several basic responses of the glomerulus to injury such as cellular proliferation, changes in glomerular cell phenotypes, and increased deposition of extracellular matrix. The site of glomerular cell injury defines the clinical presentation. This chapter aims at presenting a brief overview over the phenomenal advances in our understanding of glomerular cell biology in health and disease over the last decade, which hopefully soon translates into better therapeutic options for progressive glomerular and renal kidney disease.