Cyclin I protects podocytes from apoptosis.

The limited regenerative capacity of the glomerular podocyte following injury underlies the development of glomerulosclerosis and progressive renal failure in a diverse range of kidney diseases. We discovered that, in the kidney, cyclin I is uniquely expressed in the glomerular podocyte, and have constructed cyclin I knock-out mice to explore the biological function of cyclin I in these cells. Cyclin I knock-out (-/-) podocytes showed an increased susceptibility to apoptosis both in vitro and in vivo.

Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins.

Nephrotic-range proteinuria is due to glomerular diseases characterized by podocyte injury. Glucocorticoids are the standard of care for most forms of nephrotic syndrome. However, the precise mechanisms underlying the beneficial effects of glucocorticoids on podocytes, beyond its general immunosuppressive and anti-inflammatory effects, are still unknown.

ATRA induces podocyte differentiation and alters nephrin and podocin expression in vitro and in vivo.

Background: Podocytes are terminally differentiated and highly specialized epithelial cells. The factors governing podocyte differentiation are poorly understood. We tested the hypothesis that all-trans retinoic acid (ATRA), a vitamin A derivative, induces podocyte differentiation in vitro and in vivo.

Limitation of podocyte proliferation improves renal function in experimental crescentic glomerulonephritis.

Background: Many forms of glomerular diseases are characterized by injury to the glomerular visceral epithelial cell, or podocyte, which usually results in depletion of podocyte number. However, in diseases where podocyte proliferation occurs there is a rapid decline in renal function. The consequences of inhibiting podocyte proliferation on renal function have not been fully established.

Cyclin-dependent kinase 5 is a regulator of podocyte differentiation, proliferation, and morphology.

Podocytes are highly specialized and terminally differentiated glomerular cells that play a vital role in renal physiology, including the prevention of proteinuria. Cyclin-dependent kinase 5 (CDK5) has been shown to influence several cellular processes in other terminally differentiated cells, in particular neurons. In this study, we examined the role of CDK5 in podocyte differentiation, proliferation, and morphology.

The role of cell cycle proteins in Glomerular disease.

Although initially identified and characterized as regulators of the cell cycle and hence proliferation, an extended role for cell cycle proteins has been appreciated more recently in a number of physiologic and pathologic processes, including development, differentiation, hypertrophy, and apoptosis. Their precise contribution to the cellular response to injury appears to be dependent on both the cell type and the nature of the initiating injury. The glomerulus offers a remarkable situation in which to study the cell cycle proteins, as each of the 3 major resident cell types (the mesangial cell, podocyte, and glomerular endothelial cell) has a specific pattern of cell cycle protein expression when quiescent and responds uniquely after injury.

Podocyte proliferation and differentiation in glomerular disease: role of cell-cycle regulatory proteins.

Injury to the podocyte underlies many forms of glomerular disease. In contrast to mesangial and endothelial cells, podocytes do not typically proliferate. Moreover, the lack of proliferation is thought to underlie the development of glomerulosclerosis.

Accelerated progression of calcific aortic stenosis in dialysis patients.

Background: Abnormalities of the aortic valve occur with increased frequency in patients with renal failure and may contribute to the observed excess cardiovascular mortality. Little data exist on the rate at which aortic stenosis progresses in this patient group.

Methods: A retrospective case-control study was designed to compare the rate of progression of aortic stenosis in dialysis patients with that in sex-matched controls.

Cell cycle control in glomerular disease.

The sequential activation of the cyclin-dependent kinases by their partner cyclins underlies the progression of the cell cycle from quiescence through growth to cell division. More recently a role for these proteins and their inhibitors has been appreciated in several diverse renal and non-renal cell processes, including proliferation, development, differentiation, hypertrophy and apoptosis. The glomerulus represents a unique micro-environment in which to study the cellular outcome following injury, as each of the three resident cell types undergoes a specific and distinct response to a given stimulus.