Figure 3.

Reversible and irreversible consequences of dysregulated podocyte signaling. (a) Dysregulated signaling at the plasma membrane may lead to reversible morphological changes. Therefore, proteinuria may arise, with or without foot process (FP) effacement (see text for details). However, if the upstream injurious signals are reversed, the cell morphology can revert back to physiological patterns. SD denotes slit diaphragm. (b) Persistence of podocyte injury is manifest in the activation of cellular processes that lead to irreversible changes such as loss of adhesion to the glomerular basement membrane (GBM), cell hypertrophy, transcriptional changes, disrupted metabolic pathways, autophagy, and cell cycle dysregulation. These irreversible changes can cause podocyte cell death or the detachment of podocytes from the GBM. Podocyte senescence may also be a manifestation of persistent injury, although less is known about this mechanism. The resulting loss of podocytes ultimately leads to irreversible glomerulosclerosis and kidney failure.