Podocalyxin

BACKGROUND: Membranous nephropathy (MN) is one of the cardinal causes of nephrotic syndrome in adults, but an adequate treatment regimen is lacking. PURPOSE: We assessed the effect of Moshen granule (MSG) on patients with MN and cationic bovine serum albumin (CBSA)-induced rats. We further identified the bioactive components of MSG and revealed the underlying molecular mechanism of its renoprotective effects. METHODS: We determined the effect of MSG on patients with MN and CBSA-induced rats and its components on podocyte injury in zymosan-activated serum (ZAS)-elicited podocytes and revealed their regulatory mechanism on the Wnt/β-catenin/renin-angiotensin system (RAS) signalling axis...

OBJECTIVE: To assess renal injury in an arginine vasopressin (AVP) rodent model of preeclampsia. STUDY DESIGN: Urinary expression of kidney injury molecule-1 (KIM-1), urinary protein and creatinine was determined in rodents (n = 24; pregnant AVP, pregnant saline, non-pregnant AVP and non-pregnant saline), which received a continuous dose of either AVP or saline via subcutaneous mini osmotic pumps for 18 days, using a Multiplex kidney toxicity immunoassay...

Podocalyxin (PCX) is an indicator of glomerular injury. Aside from the kidney, it is expressed in the endothelial cells of various organs. Echographic examinations are useful in assessing the alterations in cardiovascular structure and function during pregnancy.

OBJECTIVE: The pathogenesis of preeclampsia (PE) is known to be endothelial cell damage; however, the existence of dysfunction in glomerular endothelial glycocalyx, podocytes and tubules remains unclear. The glomerular endothelial glycocalyx, basement membrane, podocytes, and tubules are permeability barriers against albumin excretion. This study aimed to assess the relationship between urinary albumin leakage and injuries of the glomerular endothelial glycocalyx, podocytes, and tubules in patients with PE...

BACKGROUND: Diabetic kidney disease (DKD) is a serious complication that begins with albuminuria and often leads to a rapid progressive decline in renal function. Niclosamide is a potent inhibitor of the Wnt/β-catenin pathway, which controls the expression of multiple genes of the renin-angiotensin-aldosterone system (RAAS), which in turn is influences the progression of DKD. This study was conducted to evaluate the effect of niclosamide as adjuvant therapy on DKD. METHODS: Out of 127 patients screened for eligibility, 60 patients completed the study...

The glycocalyx component and sialomucin podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumor types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression of integrin-based invasion...

Dent disease (DD1) is a rare tubulopathy caused by mutations in the CLCN5 gene. Glomerulosclerosis was recently reported in DD1 patients and ClC-5 protein was shown to be expressed in human podocytes. Nephrin and actin cytoskeleton play a key role for podocyte functions and podocyte endocytosis seems to be crucial for slit diaphragm regulation. The aim of this study was to analyze whether ClC-5 loss in podocytes might be a direct consequence of the glomerular damage in DD1 patients. Three DD1 kidney biopsies presenting focal global glomerulosclerosis and four control biopsies were analyzed by immunofluorescence (IF) for nephrin and podocalyxin, and by immunohistochemistry (IHC) for ClC-5...

RATIONALE & OBJECTIVE: Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD. STUDY DESIGN: Observational cohort. SETTING & PARTICIPANTS: 118 consecutive patients with biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls...

The definition of acute kidney injury (AKI), despite improvements in criteria, continues to be based on the level of serum creatinine and urinary output that do not specifically indicate tubular function or injury, or glomerular function or injury that is not significant enough to warrant acute hospitalization of the patient. Finding novel biomarkers of AKI has become a major focus nowadays in nephrology to overcome the further complications of end stage renal disease (ESRD). Many compounds, such as KIM 1, IL 18, NGAL, uromodulin, calprotectin, vanin 1, galactin 3, platelet-derived growth factor (PDGF), urinary Na+ /H+ exchanger isoform 3 (NHE3), retinol binding protein (RBP) and Cystatin C, are released from the renal tubules and thus any alterations in tubular function can be detected by measuring these parameters in urine...

Finding the ideal epitope to target is a key element for the development of an antibody-drug conjugate (ADC). To maximize drug delivery to tumor cells and reduce side effects, this epitope should be specific to cancer cells and spare all normal tissue. During cancer progression, glycosylation pathways are frequently altered leading to the generation of new glycosylation patterns selective to cancer cells. Mucins are highly glycosylated proteins frequently expressed on tumors and, thus, ideal presenters of altered glycoepitopes...

Diabetic nephropathy is one of the most serious microvascular complications of diabetes mellitus, with increasing prevalence and mortality. Currently, renal function is assessed clinically using albumin excretion rate and glomerular filtration rate. But before the appearance of micro-albumin, the glomerular structure has been severely damaged. Glomerular filtration rate based on serum creatinine is a certain underestimate of renal status. Early diagnosis of diabetic nephropathy has an important role in improving kidney function and delaying disease progression with drugs...

This study's objective is to evaluate the correlation relationship between Podocalyxin (PCX), an urinary marker of podocytes, urinary albumin-creatinine ratio (ACR) and the predictive value of PCX in the routine screen of early diabetic kidney disease (DKD) among older people. We also aimed to explore its prediction value despite of other metabolic factor and how PCX alters in the predictive power for early stage of diabetic nephropathy. In retrospective, 320 cases of older patients diagnosed with type 2 diabetes mellitus who met both inclusion and exclusion criteria were collected and divided with levels of urinary albumin, that is, normal albuminuria group, microalbuminuria group and healthy group...

Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts...

In this study, we characterized a series of antibodies generated in C57BL/6 mice (Mus musculus) using the Tic (JCRB1331) human induced pluripotent cell (hiPSC) line as an antigen. This report describes the isolation and characterization of two new antibodies, R-6C (IgM) and R-13E (IgM), and their comparisons with two existing antibodies, R-10G (IgG1) and R-17F (IgG1). Their epitopes were studied by Western blotting after various glycosidase digestions, binding analyses using enzyme-linked immunosorbent assays (ELISAs) and microarrays with various synthetic oligosaccharides...

Tumor-associated tertiary lymphoid structures are ectopic lymphoid aggregates that have considerable morphological, cellular, and molecular similarity to secondary lymphoid organs, particularly lymph nodes. Tumor vessels expressing peripheral node addressin (PNAd) are hallmark features of these structures. Previous work from our laboratory demonstrated that PNAd is displayed on intratumoral vasculature of murine tumors, and its expression is controlled by the engagement of lymphotoxin-α3 , secreted by effector CD8 T cells, with tumor necrosis factor receptors (TNFR) on tumor endothelial cells (TEC)...

Establishment of endometrial surface receptivity is crucial for the initiation of embryo implantation, yet the molecular mechanisms are not well understood especially in the human. We have recently discovered that podocalyxin (PODXL) is a critical negative regulator of human endometrial surface receptivity. PODXL is highly expressed in all epithelial and endothelial cells in the non-receptive endometrium, but down-regulated specifically in the luminal epithelium at receptivity. We have further shown that PODXL inhibits embryo implantation, and that PODXL down-regulation is essential for endometrial surface receptivity...

BACKGROUND AND AIMS: Low-grade chronic inflammation was reported to serve as a distinctive pathophysiologic feature of coronary artery disease (CAD), the leading cause of death around the world. Herein, the current study aimed to explore whether and how microRNA-34c-5p (miR-34c-5p), a miRNA enriched in extracellular vesicles (EVs) originated from the activated platelet (PLT-EVs), affects the inflammation of human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: HCAECs were established as an in vitro cell model using oxidized low-density lipoprotein (ox-LDL)...

Chlorogenic acid (CGA) is a highly abundant bioactive compound in green coffee beans. CGA has protective roles in various cardiovascular diseases, suggesting that it may affect endothelial cells lining the blood vessels. However, cellular mechanisms underlying its beneficial effects remained unclear. We therefore performed quantitative proteomics of CGA-treated human endothelial cells, followed by enrichment/pathway analyses, and functional validation using various assays. EA.hy926 cells were treated with 5 µM CGA for 24-h before nanoLC-LTQ-Orbitrap MS/MS analyses...

BACKGROUND: Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus and a primary reason for end-stage renal disease (ESRD). Isorhapontigenin (ISO), a natural derivative of stilbene, has significant anti-inflammatory and antioxidant effects. Nevertheless, its impact on DN remains elusive. METHODS: Human vascular endothelial cells (HUVECs) and podocytes were damaged by high glucose (HG). Cell viability and apoptosis were testified by the cell counting kit-8 (CCK-8) assay and flow cytometry, respectively...

Since gastric cancer is the second leading cause of cancer deaths worldwide, more understanding of its molecular basis is urgently needed. Gastric gland mucin secreted from pyloric gland cells, mucous neck cells, and cardiac gland cells of the gastric mucosa harbors unique O-glycans carrying terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). We previously reported that αGlcNAc loss correlated positively with poor outcomes for patients with differentiated-type gastric cancer. However, the molecular mechanisms underlying these outcomes remained poorly understood...