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Fetal podocyte

Mazène Hochane, Patrick R van den Berg, Xueying Fan, Noémie Bérenger-Currias, Esmée Adegeest, Monika Bialecka, Maaike Nieveen, Maarten Menschaart, Susana M Chuva de Sousa Lopes, Stefan Semrau
The current understanding of mammalian kidney development is largely based on mouse models. Recent landmark studies revealed pervasive differences in renal embryogenesis between mouse and human. The scarcity of detailed gene expression data in humans therefore hampers a thorough understanding of human kidney development and the possible developmental origin of kidney diseases. In this paper, we present a single-cell transcriptomics study of the human fetal kidney. We identified 22 cell types and a host of marker genes...
February 21, 2019: PLoS Biology
Bin Li, Yanan Zhu, Haiyun Chen, Hui Gao, Hangyuan He, Na Zuo, Linguo Pei, Wen Xie, Liaobin Chen, Ying Ao, Hui Wang
This study aimed to demonstrate that prenatal dexamethasone exposure (PDE) can induce kidney dysplasia in utero and adult glomerulosclerosis in male offspring, and to explore the underlying intrauterine programming mechanisms. Pregnant rats were subcutaneously administered dexamethasone 0.2 mg/kg.d from gestational day (GD) 9 to GD20. The male fetus on GD20 and the adult offspring at age of postnatal week 28 were analyzed. The adult offspring kidneys in the PDE group displayed glomerulosclerosis, elevated levels of serum creatinine and urine protein, ultrastructural damage of podocytes, the reduced expression levels of podocyte marker genes, nephrin and podocin...
October 22, 2018: Toxicology
Caroline Rauch, Elisabeth Feifel, Georg Kern, Cormac Murphy, Florian Meier, Walther Parson, Mario Beilmann, Paul Jennings, Gerhard Gstraunthaler, Anja Wilmes
Podocytes play a critical role in glomerular barrier function, both in health and disease. However, in vivo terminally differentiated podocytes are difficult to be maintained in in vitro culture. Induced pluripotent stem cells (iPSCs) offer the unique possibility for directed differentiation into mature podocytes. The current differentiation protocol to generate iPSC-derived podocyte-like cells provides a robust and reproducible method to obtain podocyte-like cells after 10 days that can be employed in in vitro research and biomedical engineering...
2018: PloS One
Ya-Nan Zhu, Ying Ao, Bin Li, Yang Wan, Hui Wang
Podocyte is one of the main components of glomerular filtration barrier in the kidney; the loss or dysfunction of podocyte could impair the functions of glomerular filtration barrier, leading to development of various renal diseases. Podocyte is a terminally differentiated cell, and thus does not possess any proliferative properties. Accordingly, its number and contribution to renal function are initially determined by its normal development. Information from the literature and results of our research indicate that genetic factors or prenatal adverse environment could cause developmental retardation of podocytes, thereby suggesting the potential fetal developmental origin(s) of kidney diseases, and involvement of epigenetic mechanisms in the regulation of key genes in podocyte development...
February 20, 2018: Yi Chuan, Hereditas
Marija Dakovic Bjelakovic, Slobodan Vlajkovic, Milica Bjelakovic
The aim of this study was to determine the developmental characteristics of podocytes in the human fetal metanephros using scanning electron microscopy, light microscopy, and transmission electron microscopy. Kidney samples of 15 human fetuses of both sexes (gestational age 10-22 weeks) were analyzed. At the S-shaped body stage, primitive podocytes were arranged in a layer of cuboidal cells beneath the vascular cleft. When observed from Bowman's space, the demarcation between adjacent podocytes was not clear, but mild depressions indicated cell boundaries...
2018: Cells, Tissues, Organs
Danica Ryan, Megan R Sutherland, Tracey J Flores, Alison L Kent, Jane E Dahlstrom, Victor G Puelles, John F Bertram, Andrew P McMahon, Melissa H Little, Lynette Moore, Mary Jane Black
BACKGROUND: During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS: Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined...
January 2018: EBioMedicine
Eishin Yaoita, Yutaka Yoshida, Masaaki Nameta, Hiroki Takimoto, Hidehiko Fujinaka
Highly organized cell processes characterize glomerular podocytes in vivo. However, podocytes in culture have a simple morphology lacking cell processes, especially upon reaching confluence. Here, we aimed to establish culture conditions under which cultured podocytes extend cell processes at confluence. Among various culture conditions that could possibly cause phenotypic changes in podocytes, we examined the effects of heparin, all-trans retinoic acid, fetal bovine serum, and extracellular matrices on the morphology of podocytes in rat primary culture...
February 2018: Kidney International
Sarwat I Gilani, Ulrik Dolberg Anderson, Muthuvel Jayachandran, Tracey L Weissgerber, Ladan Zand, Wendy M White, Natasa Milic, Maria Lourdes Gonzalez Suarez, Rangit Reddy Vallapureddy, Åsa Nääv, Lena Erlandsson, John C Lieske, Joseph P Grande, Karl A Nath, Stefan R Hansson, Vesna D Garovic
Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma...
November 2017: Journal of the American Society of Nephrology: JASN
Taihei Hayashi, Shuko Tokuriki, Takashi Okuno, Genrei Ohta, Aiko Igarashi, Yusei Ohshima
BACKGROUND: The number of nephrons at birth is determined during fetal development and is modulated thereafter by postnatal podocyte injury. Hyperfiltration, caused by a reduced number of nephrons, is a risk factor for chronic kidney disease. It is therefore important to monitor the formation of nephrons. METHODS: Urine samples were collected from infants within 1-2 days of birth, with follow-up sampling for preterm infants at 37-39 weeks of corrected age. Urinary levels of podocalyxin (PCX), β2-microglobulin (β2MG), N-acetyl-ß-D-glucosaminidase (NAG), total protein (TP), microalbumin (mAlb) and creatinine were measured and the relationship between these markers evaluated...
October 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Anastasia Logothetidou, Ward De Spiegelaere, Wim Van den Broeck, Tim Vandecasteele, Liesbeth Couck, Paul Simoens, Pieter Cornillie
Angiopoietins and their TIE receptors are important regulators of vascular stability and remodeling. These molecules are involved not only in the normal development of kidney glomeruli, but also in disease, thus making them promising targets for therapies. Although TIE receptors are mainly found in endothelial cells, some reports observed TIE2 expression in glomerular podocytes as well. This suggests a role of angiopoietins in the regulation of podocytes. In the present study, we aimed to map the subcellular localization of TIE receptors in metanephric glomeruli of fetal pigs using high-resolution immunogold electron microscopy and the relative labeling index stereological approach...
June 2017: Micron: the International Research and Review Journal for Microscopy
Hisashi Takagi, Yukino Nishibori, Kan Katayama, Tomohisa Katada, Shohei Takahashi, Zentaro Kiuchi, Shin-Ichiro Takahashi, Hiroyasu Kamei, Hayato Kawakami, Yoshihiro Akimoto, Akihiko Kudo, Katsuhiko Asanuma, Hiromu Takematsu, Kunimasa Yan
Unbiased transcriptome profiling and functional genomics approaches have identified ubiquitin-specific protease 40 (USP40) as a highly specific glomerular transcript. This gene product remains uncharacterized, and its biological function is completely unknown. Here, we showed that mouse and rat glomeruli exhibit specific expression of the USP40 protein, which migrated at 150 kDa and was exclusively localized in the podocyte cytoplasm of the adult kidney. Double-labeling immunofluorescence staining and confocal microscopy analysis of fetal and neonate kidney samples revealed that USP40 was also expressed in the vasculature, including in glomerular endothelial cells at the premature stage...
April 1, 2017: American Journal of Physiology. Renal Physiology
Anastasia Logothetidou, Tim Vandecasteele, Els Van Mulken, Kimberley Vandevelde, Pieter Cornillie
Intussusceptive angiogenesis (IA) is required for normal embryonic vascular development. The Tie family of receptors and their ligands, the angiopoietins, play an important role in the growth or regression of blood vessels which are important not only during development but also throughout an organism's life. The presence of IA was investigated in glomerular capillaries of the fetal porcine metanephros using Mercox II resin casts. The first signs of IA were observed in stage III glomeruli. Stage IV and V glomeruli showed numerous signs of aligned pillar formation and their successive merging to delineate the vascular entities...
August 2017: Histology and Histopathology
Whitney Besse, Sherry Mansour, Karan Jatwani, Cynthia C Nast, Ursula C Brewster
BACKGROUND: Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG...
September 6, 2016: BMC Nephrology
Leslie A Bruggeman, Zhenzhen Wu, Liping Luo, Sethu M Madhavan, Martha Konieczkowski, Paul E Drawz, David B Thomas, Laura Barisoni, John R Sedor, John F O'Toole
APOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes...
December 2016: Journal of the American Society of Nephrology: JASN
Dafni Moschidou, Michelangelo Corcelli, Kwan-Leong Hau, Victoria J Ekwalla, Jacques V Behmoaras, Paolo De Coppi, Anna L David, George Bou-Gharios, H Terence Cook, Charles D Pusey, Nicholas M Fisk, Pascale V Guillot
Alport syndrome (AS) is a hereditary glomerulopathy caused by a mutation in type IV collagen genes, which disrupts glomerular basement membrane, leading to progressive glomerulosclerosis and end-stage renal failure. There is at present no cure for AS, and cell-based therapies offer promise to improve renal function. In this study, we found that human first trimester fetal chorionic stem cells (CSC) are able to migrate to glomeruli and differentiate down the podocyte lineage in vitro and in vivo. When transplanted into 7-week-old Alport 129Sv-Col4α3(tm1Dec)/J (-/-) mice, a single intraperitoneal injection of CSC significantly lowered blood urea and urine proteinuria levels over the ensuing 2 weeks...
March 1, 2016: Stem Cells and Development
Minoru Takasato, Pei X Er, Han S Chiu, Barbara Maier, Gregory J Baillie, Charles Ferguson, Robert G Parton, Ernst J Wolvetang, Matthias S Roost, Susana M Chuva de Sousa Lopes, Melissa H Little
The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins...
October 22, 2015: Nature
Yogavijayan Kandasamy, David Watson, Donna Rudd
OBJECTIVES: Nephrin is an integral part of podocytes that together with endothelial cells and the basement form the glomerular filtration barrier. Placental ischemia triggers a cascade of events that ultimately result in endothelial malfunction, hypertension, podocytopathy and fetal compromise. METHODS: We review the literature to determine if urine nephrin measurements could serve as a useful biomarker to detect early podocyte injury in pre-eclampsia. RESULTS: Our search identifies eight studies published to date...
November 2015: Hypertension in Pregnancy
Bo Hyon Yun, Seung Mi Lee, Hee Young Cho, Ji Young Kim, Ga Hyun Son, Young Han Kim, Yong Won Park, Beom Jin Lim, Ja Young Kwon
Nephrin is the signature molecule in the podocyte of the glomerulus that forms the renal slit diaphragm, the main functional unit of the glomerulus. The present study focused on the expression of nephrin in the human placenta, which may also have a role in filtration and the maintenance of homeostasis in the kidneys. A total of nine placentas from normal healthy pregnant females at full term were investigated. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were performed...
October 2015: Molecular Medicine Reports
M Penning, T Kelder, H-W Uh, D Cohen, S Scherjon, J A Bruijn, K Bloemenkamp, H Baelde
INTRODUCTION: Preeclampsia affects 5% of all pregnancies and is a significant cause of maternal and fetal morbidity and mortalityworldwide. A clinically useful screening test that can predict the development of preeclampsia at an early stage is urgently needed. The detection of podocyturia by immunohistochemistry following cell culture has been noted as a sensitive and specific marker for preeclampsia. However, this method is laborious and carries the risk of cell-culture contamination...
July 2012: Pregnancy Hypertension
Ying Ao, Zhaoxia Sun, Shuangshuang Hu, Na Zuo, Bin Li, Shuailong Yang, Liping Xia, Yong Wu, Linlong Wang, Zheng He, Hui Wang
Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized...
September 1, 2015: Toxicology and Applied Pharmacology
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