Podocyte Markers

 

 

 

Podocytes (or visceral epithelial cells) are cells of the visceral epithelium in the kidneys and form a crucial component of the glomerular filtration barrier, contributing size selectivity and maintaining a massive filtration surface.

 

 

 

The 13A antigen

  • an integral membrane protein of several rat epithelial tissues and cultured cells, and is particularly abundant in the podocyte foot processes. Although its identity and function remain unknown, the 13A protein is a valuable marker for the basal membrane domain of the podocyte. PMID: 7967507

alpha-actinin-4

  • interacts with integrins and strengthens the podocyte-GBM interaction thereby stabilizing glomerular architecture and preventing disease. PMID: 17082197

B7-1

  • B7-1 in podocytes was found in genetic, drug-induced, immune-mediated, and bacterial toxin-induced experimental kidney diseases with nephrotic syndrome. The clinical significance of our results is underscored by the observation that podocyte expression of B7-1 correlated with the severity of human lupus nephritis. PMID: 15146236

  • damaged podocyte marker. PMID: 16636193

CD2AP

  • highly expressed in podocytes and is considered to play an important role in the maintenance of the glomerular slit diaphragm. PMID: 17213204, PMID: 15951437, PMID: 11733379

  • CD2AP seems to be involved in the regulation of highly dynamic F-actin structures in podocyte foot processes. PMID: 11553524

CD10

Cortactin

  • a podocyte protein. PMID: 15200416

  • Immunofluorescence labeling for actin-binding proteins in immature podocyte showed that alpha-actinin was localized at the level of the junctional complex, whereas cortactin was distributed beneath the entire plasmalemma. PMID: 14623927

Desmin

Dystroglycan (DG)

  • Podocyte structure-related gene. PMID: 17003339

  • In the kidney, dystroglycan (DG) has been shown to cover the basolateral and apical membranes of the podocyte. alpha-DG is heavily glycosilated, which is important for its binding to laminin and agrin in the glomerular basement membrane. PMID: 16672922

  • alpha-DG covers the whole podocyte cell membrane in the rat, and is expressed at both the basolateral and apical sides of the podocyte. This localization suggests that alpha-DG plays a dual role in the maintenance of the unique architecture of podocytes by its binding to the glomerular basement membrane, and in the maintenance of the integrity of the filtration slit, respectively. PMID: 15956031

  • The antibodies against alpha- and beta-dystroglycan and utrophin revealed a granular podocyte-like staining pattern along the glomerular capillary wall. With immunoelectron microscopy, agrin was found in the glomerular basement membrane, dystroglycan was diffusely found over the entire cell surface of the podocytes, and utrophin was localized in the cytoplasm of the podocyte foot processes. PMID: 10793086

Ezrin

  • a potent marker of podocyte injury (podocytopathy) and may help in the histological qualification of Minimal change disease (MCD), diffuse mesangial proliferation (DMP) and focal segmental glomerulosclerosis (FSGS). The increased permeability of the filtration barrier in steroid-resistant and proteinuric glomerulopathies may be a consequence of subcellular changes in podocyte-associated proteins following decreased expression of ezrin. PMID: 16522749

  • ezrin protein (by immunohistochemistry) was specifically and exclusively modulated during podocyte injury and regeneration. Ezrin immunohistochemistry was able to visualize cell body attenuation, pseudocysts, and in particular vacuolation of injured podocytes, a feature that usually has to be identified at the ultrastructural level, and was strikingly increased in binucleated podocytes or podocytes that were partially or completely detached from the underlying GBM (frequently also binucleated). Infiltrating macrophages also express ezrin, but can easily be differentiated from podocytes by their round shape and higher level of expression. Since suitable light microscopic markers for the identification of glomerular epithelial cells are rare, ezrin may also be a useful marker for podocytes in normal and injured glomeruli. PMID: 9853258

FAT

GLEPP1 (Glomerular epithelial protein 1)

  • a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes, is a useful marker of acute podocyte injury. PMID: 11961407

Lmx1b

  • a podocyte protein. PMID: 15200416

  • play a role for in the regulation of collagen IV expression and in the transcriptional regulation of podocyte specification and differentiation. PMID: 12602071

  • the LIM homeodomain transcription factor, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. PMID: 11978876

  • regulates the expression of multiple podocyte genes critical for podocyte differentiation and function. PMID: 11956244

MAP-LC3 (Microtubule-associated protein 1 light chain 3)

  • especially expressed in the podocytes of rat kidney as the membrane-bound form LC3-II. Biochemical analysis using a conditionally immortalized mouse podocyte clone (MPC) revealed that LC3-I is processed to LC3-II during the differentiation of cells into mature podocytes and accumulates in the membrane-rich fraction of the cell lysate. LC3-II-localized vesicles play an important role in the physiological function of podocytes. PMID: 12709412

Myocilin

  • a 55 to 57 kD secreted glycoprotein and member of the olfactomedin protein family, is expressed in podocytes of the kidney and induced in mesangial cells during experimental mesangioproliferative glomerulonephritis. PMID: 15610237

NEPH1

Nephrin

  • The major podocyte protein, is podocyte specific marker and has a crucial role in the filtration barrier of the glomerular podocyte. PMID: 15579507, PMID: 15996647

  • a crucial podocyte molecule in the kidney glomerular filtration barrier and it is also expressed in Langerhans islet beta cells of the pancreas. PMID: 16841182

  • Nephrin is an Ig-like transmembrane protein. It is a major component of the podocyte slit diaphragm and is essential for maintaining normal glomerular permeability. PMID: 11880318

  • a new protein of the interpodocyte filtration slit area with a profound role in the pathophysiology of the filtration barrier. PMID: 10550324

  • a crucial podocyte molecule in the kidney glomerular filtration barrier and it is also expressed in Langerhans islet beta cells of the pancreas. PMID: 16841182

P-cadherin

PHM-5 (podocalyxin-like protein in humans)

Podocin

Podoplanin

  • a glomerular podocyte membrane mucoprotein. PMID: 16773315, PMID: 16209358

  • a rat podocyte protein, plays a role in maintaining the unique shape of podocytes. PMID: 12032185

  • The 43-kD integral membrane protein podoplanin is localized on the surface of rat podocytes, and transcriptionally downregulated in rat puromycin nephrosis. Podoplanin plays a role in maintaining the unique shape of podocyte foot processes and glomerular permeability. PMID: 9808087

Podocalyxin (PC)

  • the major sialoglycoprotein expressed on the apical membrane of the podocyte. PMID: 15339978

  • a well-known podocyte specific marker, was initially identified as a major sialoprotein on the apical surface of glomerular podocytes to perform the filtration barrier function. Later, it was reported to be expressed in endothelial cells, megakaryotes/platelets, and hemangioblasts, the common progenitor cells of the hematopoietic and endothelial cells. PMID: 17180683

Synaptopodin

T-/H-cadherin (CDH13)

VEGF

  • DDS (Denys-Drash syndrome) podocytes express high levels of the proangiogenic isoform VEGF165, but completely lack the inhibitory isoform VEGF165b. PMID: 17267748

  • play a role in maintaining the podocyte function as well as renal vasculature, thereby protecting glomeruli and interstitium from progressive renal insults. PMID: 16641924

  • Vascular endothelial growth factor (VEGF)-A is an autocrine survival factor for podocytes, which express two VEGF receptors, VEGF-R1 and VEGF-R3. PMID: 16525158

  • a key role for VEGF-A production in the podocyte for mesangial cell survival and differentiation. PMID: 16436493

  • VEGF is both produced by and acts upon the podocyte in an autocrine manner to modulate podocyte function, including the synthesis of GBM components. PMID: 15919782

  • In non-sclerosed glomeruli (within podocyte cytoplasm), VEGF-C1 was more expressed in podocytes of all groups (P < 0.0002), while the distribution of synaptopodin was less expressed in all groups (P < 0.0002). PMID: 15693890

Vimentin

  • marker of podocyte maturity. PMID: 12119471, PMID: 9377221  

  • well-established marker protein of podocytes. PMID: 11473645

  • the podocyte intermediate cytoskeletal protein. PMID: 11086029

  • In control rats, tubulin and vimentin were present, limited to the podocyte cell body and the major processes. PMID: 7952147

  • Vimentin and tubulin, the main protein subunits of intermediate filaments and microtubules, respectively, were confined to the podocyte cell body and the major processes but were virtually absent from the foot processes. PMID: 3141719

Wilms' tumor-1 protein (WT-1)

ZO-1 (zonula occludens-1)

  • a junctional protein involved in the assembly and proper function of a number of tight junctions and is also expressed at the junction of podocytes with the slit diaphragm. PMID: 16567508

  • physically associated with actin in murine podocytes. PMID: 16565484

Other

  • immunostaining kidney sections with anti-C3bR antibody and urinary sediments with anti-PCX, anti-C3bR, and anti-Int alpha3 antibodies might be useful in detecting podocyte injury. PMID: 9502567