(e) Representative micrographs of immunostaining for podocin, a component ofthepodocyte slit diaphragm. Bar graphs show the quantitative evaluation of podocin staining in the glomeruli.
By forming foot processes and slit diaphragms, podocytes play central roles to prevent albuminuria in a normal state.
Via the slit diaphragm, the podocytes (as previously described) act as barrier to protein based upon size.
Most characteristically, podocytes can undergo a process termed effacement, where the normal cellular architecture of the foot process is altered and results in flattening and spreading of the foot process along the GBM and disruption of the slit diaphragm. Effacement can manifest whenever the following occurs: when the slit diaphragm and its related protein-protein interactions are disrupted, when there is interference in the normal association of the foot processes with the underlying GBM, when there is reorganization of the actin cytoskeleton and its related protein-protein interactions, or when there is disruption of the normal negatively charged apical surface of the foot processes .
The damage to podocytes which are highly differentiated cells maintaining a large filtration surface through the slit diaphragms
results in proteinuria and eventually diabetic glomerulosclerosis.
One gene that has been linked with familial autosomal dominant focal segmental glomerulosclerosis is located on chromosome 19q13 (Winn et al., 1999), coding for nephrin, a key component of the slit diaphragm
of the podocyte (Alpers, 2005).
Unravelling the mechanism of glomerular ultrafiltration: nephrin a key component of the slit diaphragm
. J Am Soc Nephrol 1999; 10:2440-5.
Previous studies have confirmed that HTH can inhibit the activation of RAS system in kidneys of DN rats, reduce the loss of podocyte slit diaphragm proteins, maintain the integrity of the filtration barrier, and reduce the leakage of proteinuria [11, 12, 18, 19].
Experiments showed that the activation of this pathway may be involved in ADR-induced podocyte foot process effacement, disruption of the slit diaphragm, and consequent albuminuria .
demonstrated that VEGF regulates slit diaphragm signaling through VEGFR2-nephrin crosstalk .
Kurihara et al., "FAT is a component of glomerular slit diaphragms," Kidney International, vol.
Previous studies considered podocin as an important slit diaphragm
protein [6,7] and that its low expression is related to the severity of proteinuria .