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The podocyte cytoskeleton in health and in disease.

Mathieson PW - Clin Kidney J (2012)

Bottom Line: Therapeutic agents that are beneficial in proteinuric disease may act at least partly by restoring the cell shape via effects on the actin cytoskeleton.Drugs that have beneficial effects on podocytes can improve our ability to treat important renal diseases including diabetic nephropathy.Currently available agents can be applied in this way and the rapid progress in the study of podocytes is highlighting new therapeutic targets that can bring even more specificity.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine & Dentistry , University of Bristol, North Bristol NHS Trust , Bristol , UK ; Academic Renal Unit , Southmead Hospital , Bristol , UK.

ABSTRACT
The podocyte is a key cell in the selective filtering action of the glomerular capillary wall. Podocyte injury is of pathogenetic and prognostic significance in human glomerular disease; podocyte repair and regeneration are important therapeutic targets. In particular, podocyte function is dependent on the cells' actin cytoskeleton: this maintains their complex structure. Alterations in the actin cytoskeleton arise from a variety of genetic and acquired causes. Therapeutic agents that are beneficial in proteinuric disease may act at least partly by restoring the cell shape via effects on the actin cytoskeleton. Recent studies of podocytes in vivo and in vitro are described, highlighting clinically relevant observations and those that help us understand the ways in which we may harness nature's own mechanisms to repair and/or renew these specialized glomerular cells, with a particular focus on their actin cytoskeleton. Drugs that have beneficial effects on podocytes can improve our ability to treat important renal diseases including diabetic nephropathy. Currently available agents can be applied in this way and the rapid progress in the study of podocytes is highlighting new therapeutic targets that can bring even more specificity.

No MeSH data available.


Related in: MedlinePlus

Transmission electron micrographs of the human glomerular capillary wall. (a) shows the normal appearance: arrows indicate endothelial fenestrations, arrowheads indicate filtration slits between podocyte foot processes and asterisks indicate actin filaments in podocyte cytoplasm. Note the actin filaments focused in podocyte foot processes. (b) shows podocyte foot process effacement as seen in proteinuric states: note flattening of the actin filaments (asterisked) longitudinally associated with the loss of normal foot process architecture.
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SFS153F2: Transmission electron micrographs of the human glomerular capillary wall. (a) shows the normal appearance: arrows indicate endothelial fenestrations, arrowheads indicate filtration slits between podocyte foot processes and asterisks indicate actin filaments in podocyte cytoplasm. Note the actin filaments focused in podocyte foot processes. (b) shows podocyte foot process effacement as seen in proteinuric states: note flattening of the actin filaments (asterisked) longitudinally associated with the loss of normal foot process architecture.

Mentions: Transmission electron microscopic imaging will be more familiar to nephrologists from looking at real biopsies and shows that the normal glomerular capillary wall, on the urinary side, has a series of filtration slits between the foot processes of the podocytes (Figure 2a). It has been known for decades that a cardinal feature of the glomerular capillary wall in proteinuric states is flattening or effacement of the foot processes due to disruption of this precise organization. The key to understanding the importance of the actin cytoskeleton is the demonstration (Figure 2b) that this effacement of foot processes is associated with flattening of the actin filaments.Fig. 2.


The podocyte cytoskeleton in health and in disease.

Mathieson PW - Clin Kidney J (2012)

Transmission electron micrographs of the human glomerular capillary wall. (a) shows the normal appearance: arrows indicate endothelial fenestrations, arrowheads indicate filtration slits between podocyte foot processes and asterisks indicate actin filaments in podocyte cytoplasm. Note the actin filaments focused in podocyte foot processes. (b) shows podocyte foot process effacement as seen in proteinuric states: note flattening of the actin filaments (asterisked) longitudinally associated with the loss of normal foot process architecture.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400570&req=5

SFS153F2: Transmission electron micrographs of the human glomerular capillary wall. (a) shows the normal appearance: arrows indicate endothelial fenestrations, arrowheads indicate filtration slits between podocyte foot processes and asterisks indicate actin filaments in podocyte cytoplasm. Note the actin filaments focused in podocyte foot processes. (b) shows podocyte foot process effacement as seen in proteinuric states: note flattening of the actin filaments (asterisked) longitudinally associated with the loss of normal foot process architecture.
Mentions: Transmission electron microscopic imaging will be more familiar to nephrologists from looking at real biopsies and shows that the normal glomerular capillary wall, on the urinary side, has a series of filtration slits between the foot processes of the podocytes (Figure 2a). It has been known for decades that a cardinal feature of the glomerular capillary wall in proteinuric states is flattening or effacement of the foot processes due to disruption of this precise organization. The key to understanding the importance of the actin cytoskeleton is the demonstration (Figure 2b) that this effacement of foot processes is associated with flattening of the actin filaments.Fig. 2.

Bottom Line: Therapeutic agents that are beneficial in proteinuric disease may act at least partly by restoring the cell shape via effects on the actin cytoskeleton.Drugs that have beneficial effects on podocytes can improve our ability to treat important renal diseases including diabetic nephropathy.Currently available agents can be applied in this way and the rapid progress in the study of podocytes is highlighting new therapeutic targets that can bring even more specificity.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine & Dentistry , University of Bristol, North Bristol NHS Trust , Bristol , UK ; Academic Renal Unit , Southmead Hospital , Bristol , UK.

ABSTRACT
The podocyte is a key cell in the selective filtering action of the glomerular capillary wall. Podocyte injury is of pathogenetic and prognostic significance in human glomerular disease; podocyte repair and regeneration are important therapeutic targets. In particular, podocyte function is dependent on the cells' actin cytoskeleton: this maintains their complex structure. Alterations in the actin cytoskeleton arise from a variety of genetic and acquired causes. Therapeutic agents that are beneficial in proteinuric disease may act at least partly by restoring the cell shape via effects on the actin cytoskeleton. Recent studies of podocytes in vivo and in vitro are described, highlighting clinically relevant observations and those that help us understand the ways in which we may harness nature's own mechanisms to repair and/or renew these specialized glomerular cells, with a particular focus on their actin cytoskeleton. Drugs that have beneficial effects on podocytes can improve our ability to treat important renal diseases including diabetic nephropathy. Currently available agents can be applied in this way and the rapid progress in the study of podocytes is highlighting new therapeutic targets that can bring even more specificity.

No MeSH data available.


Related in: MedlinePlus