Critical Analysis: Studies into the Role of the Podocyte in Kidney Disease

Critical Analysis: Studies into the Role of the Podocyte in Kidney Disease

Summary

The glomerular capillary wall is comprised of the GBM i.e. glomerular basement membrane, fenestrated capillary endothelium and glomerular podocytes. Defects in any of the three components of the glomerular capillary wall can lead to proteinuria (Jonathan & Mohamed, 2010). Glomerular podocytes are terminally differentiated epithelial cells that have large cell bodies and long primary or major processes. The primary processes attach to the underlying GBM via multiple foot processes. The interdigitating foot processes of adjacent podocytes are joined laterally by slit diaphragms that bridge the intervening filtration slits. A number of proteins have been found to comprise the slit diaphragm; these include nephrin, neph1, neph2, FAT1, FAT 2, podocin, TRPC6 and tight junction proteins. Foot process effacement of glomerular podocytes is a characteristic histology finding associated with glomerular diseases affecting the podocyte. Rearrangement of the actin cytoskeleton is necessary for foot process effacement to occur. Possible molecular mechanisms underlying cytoskeletal rearrangement include phosphorylation/dephosphorylation of nephrin and cleavage of dynamin by cathepsin-L. Activation of the urokinase receptor and initiation of beta3 integrin signaling may also be involved (Jonathan & Mohamed, 2010).

Critical Analysis

The healthy kidney metabolic filters result into the urine however averts the passage of larger essential molecule together with albumin. This careful filtration arises across the glomerular capillary wall where the glomerular capillary wall, under normal circumstances is highly permeable to small solutes and water, however negligibly to other proteins of equal molecular larger or weight or albumin (Richard, Stefan & Gerhard, 2009). Flaws or deficiencies in the glomerular capillary wall bring about augmented permeability to proteins of same size or even larger and albumin, causing proteinuria. Electrical potential differences produced by transglomerular course may adjust the flux of anionic albumin athwart the glomerular capillary wall.

To better understand the biology of glomerular podocytes, it is significant to comprehend the functional and structural composition of the glomerular capillary wall. The glomerular capillary wall, in the course of which the filtrate should pass, comprises of the following 3 layers:

Fenestrated capillary endothelium, extensively coated with a layer of polyanionic glycosoaminoglycans and glycoproteins.

Glomerular basement membrane, containing heparin sulfate and other anionic glycosoaminoglycans.

Podocytes which are connected with the GBM by detached foot processes. The slit pores that is the pores between the foot processes are clogged by a slender membrane known as the slit diaphragm, which operates as an adapted adherens junction and might also be infused by anatomical pores.

Flaws in any of the three glomerular capillary wall's components can lead to proteinuria. In addition, cross-talk between podocytes and endothelial and mesangial cells are key to the maintenance of glomerular capillary wall function. As examples, the production of vascular endothelial growth factor by podocytes is necessary for the integrity of the glomerular endothelium and the up-regulation and secretion of the podocyte protein, angiopoietin-like-4 into the glomerular capillary wall causes marked proteinuria in experimental models of nephrotic syndrome.

Podocytes are terminally differentiated epithelial cells that have ...