Cell cycle and glomerular disease: a minireview.
Globally, glomerular diseases are a leading cause of chronic and end-stage renal disease. In the mature glomerulus, under normal conditions, glomerular cells have a low turnover rate. However, in disease, a variety of pathophysiological stimuli can lead to disturbances in glomerular cell biology, including toxins, immune-mediated stresses, metabolic derangements, drugs, infections, hemodynamic changes, growth factors, and cytokines. Not only does the form of injury govern the histologic and clinical manifestations of disease, but also the nature of the response to injury. This response to injury is largely cell-type specific, and the glomerulus represents a rare microcosm of the larger organism in which one can study the cellular responses of three very distinct cell types: mesangial cells, visceral epithelial cells or podocytes, and endothelial cells. These cells can undergo several cell fates in response to injury, including proliferation, de-differentiation, hypertrophy, senescence, apoptosis, or necrosis. The regulation of these responses occurs at the level of the cell cycle, coordinated by positive regulators, cyclins and cyclin-dependent kinases, and negative regulators, cyclin-dependent kinase inhibitors. There is now a large body of literature confirming the importance of cell cycle regulatory proteins in the glomerular cellular response to injury. The recent advances in cell cycle biology in diseases of the mesangial cell and the podocyte are the focus of this minireview.
Marshall
Caroline B
CB
Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Shankland
Stuart J
SJ
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D005920:Glomerular Mesangium / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006984:Hypertrophy; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology* / Q000503:physiopathology; D050199:Podocytes / Q000473:pathology