Podocyte injury and its consequences

Abstract

Podocytes maintain the glomerular filtration barrier, and the stability of this barrier depends on their highly differentiated postmitotic phenotype, which also defines the particular vulnerability of the glomerulus. Recent podocyte biology and gene disruption studies in vivo indicate a causal relationship between abnormalities of single podocyte molecules and proteinuria and glomerulosclerosis. Podocytes live under various stresses and pathological stimuli. They adapt to maintain homeostasis, but excessive stress leads to maladaptation with complex biological changes including loss of integrity and dysregulation of cellular metabolism. Podocyte injury causes proteinuria and detachment from the glomerular basement membrane. In addition to "sick" podocytes and their detachment, our understanding of glomerular responses following podocyte loss needs to address the pathways from podocyte injury to sclerosis. Studies have found a variety of glomerular responses to podocyte dysfunction in vivo, such as disruption of podocyte-endothelial cross talk and activation of podocyte-parietal cell interactions, all of which help us to understand the complex scenario of podocyte injury and its consequences. This review focuses on the cellular aspects of podocyte dysfunction and the adaptive or maladaptive glomerular responses to podocyte injury that lead to its major consequence, glomerulosclerosis.

New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL/6 Mouse Strain

“…6d, e) [30]. Foot process effacement is closely associated with abnormalities of the actin cytoskeleton, which interacts with nephrin [31,32]. These data suggest that the early phase event is related to actin filament rearrangement in podocytes from the binding of α-mNep Ab to nephrin.…”

The mTORC2/Akt/NFκB Pathway-Mediated Activation of TRPC6 Participates in Adriamycin-Induced Podocyte Apoptosis

“…The abnormalities of podocytes, particularly SD, play a key role in the development of proteinuria. Increasing evidences demonstrated that podocyte loss due to apoptosis/death or detachment from glomerular basement membrane is involved in progressive glomerulosclerosis [2]. Additionally, damage to the glomerular filter, in particular to podocytes and SD, is of crucial importance in the pathogenesis of proteinuric diseases.…”

Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptorβ2 Agonist

“…Podocytes form a portion of the glomerular filtration barrier (GFB) (Abrahamson, 2012;Nagata, 2016), and podocyte injury and effacement occur in the progression of DN (Nakamura et al, 2000;Nagata, 2016). Given the evidence from our TEM ultrastructural analysis that AC261 mitigated podocyte foot process effacement and increased podocyte density in the GFB of HFDfed mice ( Figure 4B vs. 4C, 4F), we next asked if AC261 treatment affected the expression of podocin, a key protein in the foot process slit diaphragm structure where it is part of a scaffold complex that is essential in maintaining GFB function (Kawachi et al, 2006) and in preventing foot process effacement and loss (Kawachi et al, 2006;Nagata, 2016).…”

“…Given the evidence from our TEM ultrastructural analysis that AC261 mitigated podocyte foot process effacement and increased podocyte density in the GFB of HFDfed mice ( Figure 4B vs. 4C, 4F), we next asked if AC261 treatment affected the expression of podocin, a key protein in the foot process slit diaphragm structure where it is part of a scaffold complex that is essential in maintaining GFB function (Kawachi et al, 2006) and in preventing foot process effacement and loss (Kawachi et al, 2006;Nagata, 2016). Podocin and other slit diaphragm proteins were reduced in animal DN models (Nakamura et al, 2000), human DN (Dronavalli et al, 2008), and other nephropathies (Johnstone and Holzman, 2006).…”