TRPC6, a member of the canonical transient receptor potential channel (TRPC) subfamily, is an important cation selective ion channel on podocytes. Podocytes are highly differentiated cells located on the visceral face of glomerular basement membrane and featured by numerous foot processes, on which nephrin, podocin, and TRPC6 locate. Podocytes and the slit diaphragm (SD) between adjacent foot p...

The podocyte has an essential role in glomerular function. When cultured ex vivo, podocytes do not recapitulate their in vivo phenotype. Several technical barriers have prevented isolation of podocytes from animals with sufficient yield and purity to allow genome-wide assessment of their molecular fingerprint. Boerries et al. overcame some of these barriers and characterized the transcriptome a...

The current studies used genetic fate mapping to prove that adult podocytes can be partially replenished following depletion. Inducible NPHS2-rtTA/tetO-Cre/RS-ZsGreen-R reporter mice were generated to permanently label podocytes with the ZsGreen reporter. Experimental focal segmental glomerulosclerosis (FSGS) was induced with a cytotoxic podocyte antibody. On FSGS day 7, immunostaining for the ...

BACKGROUND Upregulation of local monocyte chemoattractant protein-1 (MCP-1) production is involved in glomerular damage through macrophage recruitment and activation in diabetic nephropathy. Treatment of db/db mice with soluble receptor for advanced glycation end-products (RAGE) prevented recruitment of macrophages to the glomeruli and reduced albuminuria, suggesting that binding of ligands and...

The pathogenesis of membranous nephropathy (MN) involves in situ formation of subepithelial immune deposits that produce glomerular injury by damaging and/or activating podocytes through complement-dependent processes. C5b-9 formation and insertion into podocyte cell membranes causes glomerular injury in MN. C5b-9 in sublytic quantities stimulates podocytes to produce proteases, oxidants, prost...

Genetic evidence supports an early role for Notch signaling in the fate of podocytes during glomerular development. Decreased expression of Notch transcriptional targets in developing podocytes after the determination of cell fate suggests that constitutive Notch signaling may oppose podocyte differentiation. This study determined the effects of constitutive Notch signaling on podocyte differen...

Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeru...

The tyrosine phosphorylation of nephrin is reported to regulate podocyte morphology via the Nck adaptor proteins. The Pak family of kinases are regulators of the actin cytoskeleton and are recruited to the plasma membrane via Nck. Here, we investigated the role of Pak in podocyte morphology. Pak1/2 were expressed in cultured podocytes. In mouse podocytes, Pak2 was predominantly phosphorylated, ...

Kidney podocytes and their slit diaphragms form the final barrier to urinary protein loss. This explains why podocyte injury is typically associated with nephrotic syndrome. The present study uncovered an unanticipated novel role for costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular permselectivity. B7-1 in podocytes was found in genetic, drug-induced, immune-media...

Podocyte injury and depletion are essential events involved in the pathogenesis of diabetic nephropathy (DN). As a terminally differentiated cell, podocyte is restricted in 'post-mitosis' state and unable to regenerate. Re-entering mitotic phase will cause podocyte disastrous death which is defined as mitotic catastrophe (MC). Murine double minute 2 (MDM2), a cell cycle regulator, is widely exp...