SPARC accelerates disease progression in experimental crescentic glomerulonephritis.

Podocytopenia characterizes many forms of glomerular disease, preceding the development of glomerulosclerosis. While detachment of viable podocytes from the underlying glomerular basement membrane is an important mechanism of podocyte loss, the underlying factors involved remain unclear. Secreted protein acidic and rich in cysteine (SPARC), a matricellular protein with counteradhesive properties, is normally expressed at low levels by the podocyte but is markedly increased following podocyte injury.

Rosuvastatin protects against podocyte apoptosis in vitro.

Background: Clinical studies suggest that statins reduce proteinuria and slow the decline in kidney function in chronic kidney disease. Given a rich literature identifying podocyte apoptosis as an early step in the pathophysiological progression to proteinuria and glomerulosclerosis, we hypothesized that rosuvastatin protects podocytes from undergoing apoptosis. Regarding a potential mechanism, our lab has shown that the cell cycle protein, p21, has a prosurvial role in podocytes and there is literature showing statins upregulate p21 in other renal cells.

Inducible rodent models of acquired podocyte diseases.

Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases.

Activation of a local renin angiotensin system in podocytes by glucose.

ANG II is a critical mediator of diabetic nephropathy. Pharmacologic inhibition of ANG II slows disease progression beyond what could be predicted by the blood pressure lowering effects alone, suggesting the importance of nonhemodynamic pathways of ANG II in mediating disease. Podocyte injury and loss are cardinal features of diabetic nephropathy.

The renin-angiotensin system in glomerular podocytes: mediator of glomerulosclerosis and link to hypertensive nephropathy.

The renoprotective effects of pharmacologic inhibition of angiotensin II extend beyond the blood pressure-lowering effects alone, consistent with the observation that angiotensin II is produced locally within the kidney and mediates tissue injury through a series of nonhemodynamic effects. Podocytes are terminally differentiated epithelial cells that contribute to the filtration barrier of the kidney, but also safeguard against the development of glomerulosclerosis. Mounting evidence demonstrates that podocytes are not only a local source of angiotensin II production, but are also vulnerable to its deleterious effects, thus fueling the future development of glomerular scarring.

Podocyte injury and targeting therapy: an update.

Purpose Of Review: Podocyte injury is a central event in the development of glomerulosclerosis. This review highlights contributions from the past year to our understanding of mechanisms of podocyte injury and implications for potential treatment strategies of glomerular disease.

Recent Findings: Rearrangement of the actin cytoskeleton, the backbone linking the slit diaphragm, apical domain and sole plate, serves as a common denominator during foot process effacement.

Mechanical strain increases SPARC levels in podocytes: implications for glomerulosclerosis.

Glomerular capillary hypertension is a final common pathway to glomerulosclerosis. Because podocyte loss is an early event in the development of glomerulosclerosis, it is logical that the deleterious effects of glomerular capillary hypertension involve podocyte injury. Yet, the mechanisms by which elevated intraglomerular pressure is translated into a maladaptive podocyte response remain poorly understood.

Activation of a local tissue angiotensin system in podocytes by mechanical strain.

Background: Glomerular capillary hypertension, a common denominator in various forms of progressive glomerular disease, results in mechanical distention of the capillary tuft, and subsequent injury of the overlying podocyte layer. The mechanisms by which elevated intraglomerular pressure is translated into a maladaptive podocyte response remain poorly understood. Angiotensin II plays a central role in the pathogenesis of chronic renal injury, largely through its actions on the subtype 1 receptor.

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.

Insulin is a potent survival factor in mesangial cells: role of the PI3-kinase/Akt pathway.

Background: Elucidating the mechanisms of apoptosis is important for understanding the molecular mechanisms underlying glomerular disease. The phosphatidylinositol 3 kinase (PI3-kinase)/Akt pathway is essential for survival signaling in non-renal cells. However, little is known about the anti-apoptotic effect of insulin and the role of the PI3-kinase/Akt pathway in mesangial cells (MC) apoptosis.