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Takahiro Imaizumi, Masahiro Nakatochi, Shin'ichi Akiyama, Makoto Yamaguchi, Hiroyuki Kurosawa, Yoshiaki Hirayama, Takayuki Katsuno, Naotake Tsuboi, Masanori Hara, Shoichi Maruyama
BACKGROUND: A non-invasive diagnostic marker of membranous nephropathy (MN) is desirable. The urinary level of podocalyxin (PCX) is higher in various glomerular diseases, including MN. The aim of this study was to construct a diagnostic model of MN with the combination of urinary PCX and clinical parameters. METHODS: We performed this cross-sectional study to construct the diagnostic models for MN by using data and samples from the multicenter kidney biopsy registry of Nagoya University and its affiliated hospitals...
2016: PloS One
Emily H Stoops, Michael Hull, Michael J Caplan
Polarized epithelial cells sort newly synthesized and recycling plasma membrane proteins into distinct trafficking pathways directed to either the apical or basolateral membrane domains. While the trans-Golgi network is a well-established site of protein sorting, increasing evidence indicates a key role for endosomes in the initial trafficking of newly synthesized proteins. Both basolateral and apical proteins have been shown to traverse endosomes en route to the plasma membrane. In particular, apical proteins traffic through either subapical early or recycling endosomes...
December 2016: Traffic
Zhufeng Yang, Susan E Zimmerman, Jun Tsunezumi, Caitlin Braitsch, Cary Trent, David M Bryant, Ondine Cleaver, Consuelo González-Manchón, Denise K Marciano
Previous studies have shown CD34 family member Podocalyxin is required for epithelial lumen formation in vitro. We demonstrate that Endoglycan, a CD34 family member with homology to Podocalyxin, is produced prior to lumen formation in developing nephrons. Endoglycan localizes to Rab11-containing vesicles in nephron progenitors, and then relocalizes to the apical surface as progenitors epithelialize. Once an apical/luminal surface is formed, Endoglycan (and the actin-binding protein Ezrin) localize to large, intraluminal structures that may be vesicles/exosomes...
October 1, 2016: Developmental Biology
David Borg, Charlotta Hedner, Björn Nodin, Anna Larsson, Anders Johnsson, Jakob Eberhard, Karin Jirström
BACKGROUND: Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma. METHODS: The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment...
2016: BMC Clinical Pathology
Isabelle V Leefa Chong San, Gaëlle Prost, Jennifer A Williams, Stephen E Moss, Ulrike A Nuber
Podocalyxin (PODXL) is a highly glycosylated and sialylated transmembrane protein that is up-regulated in various types of tumors and whose expression levels positively correlate with tumor grade. We previously found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells (NSPs). Here we investigated the effects of elevated Podxl levels in these cells. NSPs overexpressing Podxl did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumor initiation...
September 16, 2016: Biochemical and Biophysical Research Communications
Paulina S Mrozowska, Mitsunori Fukuda
The characteristic feature of polarity establishment in MDCK II cells is transcytosis of apical glycoprotein podocalyxin (PCX) from the outer plasma membrane to the newly formed apical domain. This transcytotic event consists of multiple steps, including internalization from the plasma membrane, transport through early endosomes and Rab11-positive recycling endosomes, and delivery to the apical membrane. These steps are known to be tightly coordinated by Rab small GTPases, which act as molecular switches cycling between active GTP-bound and inactive GDP-bound states...
October 2016: Small GTPases
João Rodolfo Teló Timm, Cristina Karohl, Mariane Dos Santos, Maysa Lucena de Souza, Rafael Zancan, Rafael de Almeida, Francisco Veríssimo Veronese
INTRODUCTION: Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. OBJECTIVE: To evaluate if cholecalciferol supplementation reduces the levels of podocyte-associated urine mRNAs in patients with CKD. METHODS: A total of 27 patients with stages 2 to 4 CKD and suboptimal serum vitamin D [25(OH)D] levels were treated with cholecalciferol for 6 months...
June 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Li Li, Jing Wang, Yi Li, Chao Lu, Yiqing Liu, Zhifen Zhang, Zi-E Wang, Jian Zhang, Zhiming Lu
BACKGROUND: In renal diseases, earlier injury to glomerular may lead to the abscission of podocyte. The number of podocyte in urine may reflect the severity of glomerular damage. Podocalyxin (PCX) was considered as a podocyte marker. Many methods were used to detect podocyte. Applications of these methods were limited by tricky, expensive, and low accuracy. Here, we improved an immunocytochemical method to count the number of podocyte in urine. METHODS: In this study, we counted the numbers of podocyte in urine by our improved method and detected the PCX levels in urine by enzyme-linked immunosorbent assay (ELISA) in glomerulopathy patients and healthy controls...
July 20, 2016: Journal of Clinical Laboratory Analysis
Hiromi Nakao, Shogo Matsumoto, Yuko Nagai, Aya Kojima, Hidenao Toyoda, Noritaka Hashii, Daisuke Takakura, Nana Kawasaki, Tomoko Yamaguchi, Kenji Kawabata, Nobuko Kawasaki, Toshisuke Kawasaki
Recently, we established two mouse monoclonal antibodies (R-10G and R-17F). The R-17F antibody (IgG1 subtype) exhibited a strong cytotoxic effect on hiPS/ES cells. The R-17F antigen isolated from a total lipid extract of hiPS (Tic) cells was identified as LNFP I (Fucα1-2Galβ1-3GlcNAcβ1-3Galβ1-4Glc). In the present study, R-17F binding proteins were isolated from hiPS (Tic) cell lysates with an affinity column of R-17F. They gave one major R-17F positive band around 250 kDa, and several minor bands between 150 kDa and 25 kDa...
July 19, 2016: Glycoconjugate Journal
Suzy Duckworth, Melanie Griffin, Paul T Seed, Robyn North, Jenny Myers, Lucy Mackillop, Nigel Simpson, Jason Waugh, Dilly Anumba, Louise C Kenny, Christopher W G Redman, Andrew H Shennan, Lucy C Chappell
OBJECTIVE: To evaluate 47 biomarkers (selected from the current medical literature), in isolation or in combination with placental growth factor (PlGF), to determine the need for delivery within 14 days, in women presenting with suspected preterm preeclampsia. METHODS: In a prospective, multicenter observational study, 47 biomarkers were measured in 423 women presenting with suspected preterm preeclampsia (in two prespecified groups: group 1 at less than 35 weeks of gestation and group 2 presenting between 35 0/7 and 36 6/7 weeks of gestation) to evaluate their ability to determine the primary endpoint: preeclampsia requiring delivery within 14 days...
August 2016: Obstetrics and Gynecology
Claire Rigothier, Moin Ahson Saleem, Chantal Bourget, Peter William Mathieson, Christian Combe, Gavin Iain Welsh
IQGAP1, a protein that links the actin cytoskeleton to slit diaphragm proteins, is involved in podocyte motility and permeability. Its regulation in glomerular disease is not known. We have exposed human podocytes to puromycin aminonucleoside (PAN), an inducer of nephrotic syndrome in rats, and studied the effects on IQGAP1 biology and function. In human podocytes exposed to PAN, a nuclear translocation of IQGAP1 was observed by immunocytolocalization and confirmed by Western blot after selective nuclear/cytoplasmic extraction...
October 2016: Cellular Signalling
Tim Hon Man Chan, Aditi Qamra, Kar Tong Tan, Jing Guo, Henry Yang, Lihua Qi, Jaymie Siqi Lin, Vanessa Hui En Ng, Yangyang Song, Huiqi Hong, Su Ting Tay, Yujing Liu, Jeeyun Lee, Sun Yong Rha, Feng Zhu, Jimmy Bok Yan So, Bin Tean Teh, Khay Guan Yeoh, Steve Rozen, Daniel G Tenen, Patrick Tan, Leilei Chen
BACKGROUD & AIMS: Gastric cancer (GC) is the third leading cause of global cancer mortality. Adenosine-to-inosine RNA editing is a recently described novel epigenetic mechanism involving sequence alterations at the RNA but not DNA level, primarily mediated by ADAR (adenosine deaminase that act on RNA) enzymes. Emerging evidence suggests a role for RNA editing and ADARs in cancer, however, the relationship between RNA editing and GC development and progression remains unknown. METHODS: In this study, we leveraged on the next-generation sequencing transcriptomics to demarcate the GC RNA editing landscape and the role of ADARs in this deadly malignancy...
October 2016: Gastroenterology
Martin J Siemerink, Michael R Hughes, Marchien G Dallinga, Tomek Gora, Jessica Cait, Ilse M C Vogels, Bahar Yetin-Arik, Cornelis J F Van Noorden, Ingeborg Klaassen, Kelly M McNagny, Reinier O Schlingemann
The sialomucins CD34 and podocalyxin (PODXL) are anti-adhesive molecules expressed at the luminal membrane of endothelial cells of small blood vessels and facilitate vascular lumen formation in the developing mouse aorta. CD34 transcript and protein levels are increased during human angiogenesis, its expression is particularly enriched on endothelial tip cell filopodia and CD34 is a marker for tip cells in vitro. Here, we investigated whether CD34 merely marks endothelial tip cells or has a functional role in tip cells and angiogenesis...
2016: PloS One
Angélica Horrillo, Gracia Porras, Matilde S Ayuso, Consuelo González-Manchón
Podocalyxin (Podxl) has an essential role in the development and function of the kidney glomerular filtration barrier. It is also expressed by vascular endothelia but perinatal lethality of podxl(-/-) mice has precluded understanding of its function in adult vascular endothelial cells (ECs). In this work, we show that conditional knockout mice with deletion of Podxl restricted to the vascular endothelium grow normally but most die spontaneously around three months of age. Histological analysis showed a nonspecific inflammatory infiltrate within the vessel wall frequently associated with degenerative changes, and involving vessels of different caliber in one or more organs...
August 2016: European Journal of Cell Biology
Minoru Takemoto, Mayumi Shoji, Koutaro Yokote
No abstract text is available yet for this article.
April 2016: Nihon Rinsho. Japanese Journal of Clinical Medicine
Soon Hyo Kwon, John R Woollard, Ahmed Saad, Vesna D Garovic, Ladan Zand, Kyra L Jordan, Stephen C Textor, Lilach O Lerman
BACKGROUND: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). METHODS: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin-angiotensin blockade)...
May 4, 2016: Nephrology, Dialysis, Transplantation
Sang-Hoon Kim, Hyun-Jung Kim, Chan-Wha Kim
Podocyte foot processes are interdigitated to form the slit diaphragm and are crucial for the glomerular filtration barrier. Glucocorticoid-induced transcript 1 (GLCCI1) is transcriptionally regulated, but its signaling pathway in podocytes is unknown. The main objective of this study was to investigate the regulation of podocyte foot process proteins and to investigate the role of GLCCI1 in the phosphoinositide 3-kinase (PI3K) pathway using high glucose-induced podocytes and streptozotocin-induced diabetic rats...
2016: Experimental & Molecular Medicine
Anna H Larsson, Sophie Lehn, Sakarias Wangefjord, Emelie Karnevi, Eugenia Kuteeva, Magnus Sundström, Björn Nodin, Mathias Uhlén, Jakob Eberhard, Helgi Birgisson, Karin Jirström
BACKGROUND: Podocalyxin-like 1 (PODXL) is an anti-adhesive transmembrane protein that has been demonstrated to be an independent factor of poor prognosis in colorectal cancer (CRC). The gene encoding PODXL is located to chromosome 7, which also harbours the gene for the epidermal growth factor receptor (EGFR). The aim of this study was to examine the associations between PODXL and EGFR expression in CRC in vitro and in vivo. METHODS: EGFR expression was analysed in tumours from three independent patient cohorts; cohort 1 (n = 533), cohort 2 (n = 259) and cohort 3 (n = 310), previously analysed for immunohistochemical PODXL expression and KRAS and BRAF mutations (cohort 1 and 3)...
2016: Journal of Translational Medicine
Maria S Ioannou, Peter S McPherson
Development of cell polarity requires apical trafficking of podocalyxin; yet the regulation of its transport is unclear. In this issue, Mrozowska and Fukuda (2016. J. Cell Biol demonstrate that different sets of Rabs and Rab effectors are used to regulate podocalyxin trafficking in two- versus three-dimensional model systems.
May 9, 2016: Journal of Cell Biology
Paulina S Mrozowska, Mitsunori Fukuda
MDCK II cells, a widely used model of polarized epithelia, develop into different structures depending on culture conditions: two-dimensional (2D) monolayers when grown on synthetic supports or three-dimensional (3D) cysts when surrounded by an extracellular matrix. The establishment of epithelial polarity is accompanied by transcytosis of the apical marker podocalyxin from the outer plasma membrane to the newly formed apical domain, but its exact route and regulation remain poorly understood. Here, through comprehensive colocalization and knockdown screenings, we identified the Rab GTPases mediating podocalyxin transcytosis and showed that different sets of Rabs coordinate its transport during cell polarization in 2D and 3D structures...
May 9, 2016: Journal of Cell Biology
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