title: Podocyte injury and its consequences.
abstract: Podocytes maintain the glomerular filtration barrier, and the stability of this barrier depends on their highly differentiated postmitotic phenotype, which also defines the particular vulnerability of the glomerulus. Recent podocyte biology and gene disruption studies in vivo indicate a causal relationship between abnormalities of single podocyte molecules and proteinuria and glomerulosclerosis. Podocytes live under various stresses and pathological stimuli. They adapt to maintain homeostasis, but excessive stress leads to maladaptation with complex biological changes including loss of integrity and dysregulation of cellular metabolism. Podocyte injury causes proteinuria and detachment from the glomerular basement membrane. In addition to "sick" podocytes and their detachment, our understanding of glomerular responses following podocyte loss needs to address the pathways from podocyte injury to sclerosis. Studies have found a variety of glomerular responses to podocyte dysfunction in vivo, such as disruption of podocyte-endothelial cross talk and activation of podocyte-parietal cell interactions, all of which help us to understand the complex scenario of podocyte injury and its consequences. This review focuses on the cellular aspects of podocyte dysfunction and the adaptive or maladaptive glomerular responses to podocyte injury that lead to its major consequence, glomerulosclerosis.
authors.affiliation: Kidney and Vascular Pathology, University of Tsukuba, Ibaraki, Japan. Electronic address: nagatam@md.tsukuba.ac.jp.
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
mesh_terms: D017209:Apoptosis; D050476:Bowman Capsule / Q000166:cytology / Q000473:pathology; D002450:Cell Communication; D002454:Cell Differentiation; D042783:Endothelial Cells; D050533:Glomerular Basement Membrane / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology*; D006801:Humans; D018384:Oxidative Stress; D050199:Podocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000473:pathology*; D012598:Sclerosis; D013314:Stress, Mechanical
keywords: cytoskeleton; focal segmental glomerulosclerosis; podocyte; renal pathology