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https://www.readbyqxmd.com/read/28329012/tracking-the-stochastic-fate-of-cells-of-the-renin-lineage-after-podocyte-depletion-using-multicolor-reporters-and-intravital-imaging
#1
Natalya V Kaverina, Hiroyuki Kadoya, Diana G Eng, Michael E Rusiniak, Maria Luisa S Sequeira-Lopez, R Ariel Gomez, Jeffrey W Pippin, Kenneth W Gross, Janos Peti-Peterdi, Stuart J Shankland
Podocyte depletion plays a major role in focal segmental glomerular sclerosis (FSGS). Because cells of the renin lineage (CoRL) serve as adult podocyte and parietal epithelial cell (PEC) progenitor candidates, we generated Ren1cCre/R26R-ConfettiTG/WT and Ren1dCre/R26R-ConfettiTG/WT mice to determine CoRL clonality during podocyte replacement. Four CoRL reporters (GFP, YFP, RFP, CFP) were restricted to cells in the juxtaglomerular compartment (JGC) at baseline. Following abrupt podocyte depletion in experimental FSGS, all four CoRL reporters were detected in a subset of glomeruli at day 28, where they co-expressed de novo four podocyte proteins (podocin, nephrin, WT-1 and p57) and two glomerular parietal epithelial cell (PEC) proteins (claudin-1, PAX8)...
2017: PloS One
https://www.readbyqxmd.com/read/28306565/can-podocytes-be-regenerated-in-adults
#2
Stuart J Shankland, Benjamin S Freedman, Jeffrey W Pippin
PURPOSE OF REVIEW: Podocytes are critical components of the nephron filtration barrier and are depleted in many kidney injuries and disease states. Terminally differentiated adult podocytes are highly specialized, postmitotic cells, raising the question of whether the body has any ability to regenerate lost podocytes. This timely question has recently been illuminated by a series of innovative studies. Here, we review recent progress on this topic of significant interest and debate. RECENT FINDINGS: The innovation of genetic labeling techniques enables fate tracing of individual podocytes, providing the strongest evidence yet that podocytes can be replaced by nearby progenitor cells...
March 16, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28222042/compound-effects-of-aging-and-experimental-fsgs-on-glomerular-epithelial-cells
#3
Remington R S Schneider, Diana G Eng, J Nathan Kutz, Mariya T Sweetwyne, Jeffrey W Pippin, Stuart J Shankland
Advanced age portends a poorer prognosis in FSGS. To understand the impact of age on glomerular podocytes and parietal epithelial cells (PECs), experimental FSGS was induced in 3m-old mice (20-year old human age) and 27m-old mice (78-year old human age) by abruptly depleting podocytes with a cytopathic anti-podocyte antibody. Despite similar binding of the disease-inducing antibody, podocyte density was lower in aged FSGS mice compared to young FSGS mice. Activated PEC density was higher in aged versus young FSGS mice, as was the percentage of total activated PECs...
February 17, 2017: Aging
https://www.readbyqxmd.com/read/28184197/therapeutic-efficacy-of-esomeprazole-in-cotton-smoke-induced-lung-injury-model
#4
Christina Nelson, Jameisha Lee, Kang Ko, Andrew G Sikora, Mark D Bonnen, Perenlei Enkhbaatar, Yohannes T Ghebre
Proton pump inhibitors (PPIs) are well-known antacid drugs developed to treat gastric disorders. Emerging studies demonstrate that PPIs possess biological activities that extend beyond inhibition of H(+)/K(+) ATPase (proton pumps) expressed in parietal cells of the stomach. Some of the extra-gastric activities of PPIs include modulation of epithelial, endothelial, and immune cell functions. Recently, we reported that PPIs suppress the expression of several proinflammatory and profibrotic molecules, as well as enhance antioxidant mechanisms in order to favorably regulate lung inflammation and fibrosis in an animal model of bleomycin-induced lung injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28174691/beta-catenin-participates-in-dialysate-induced-peritoneal-fibrosis-via-enhanced-peritoneal-cell-epithelial-to-mesenchymal-transition
#5
Shuiyu Ji, Hao Deng, Wei Jin, Pengpeng Yan, Rending Wang, Lisha Pang, Jingyi Zhou, Jiaming Zhang, Xiaoying Chen, Xiang Zhao, Jia Shen
Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of β-catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg(-1) of the β-catenin inhibitor ICG-001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 μm ICG-001 (HG+ICG) for 48 h...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28063595/the-mitochondrial-targeted-peptide-ss-31-improves-glomerular-architecture-in-mice-of-advanced-age
#6
Mariya T Sweetwyne, Jeffrey W Pippin, Diana G Eng, Kelly L Hudkins, Ying Ann Chiao, Matthew D Campbell, David J Marcinek, Charles E Alpers, Hazel H Szeto, Peter S Rabinovitch, Stuart J Shankland
Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 months (equivalent to a 79-year-old human). To test the hypothesis that reducing mitochondrial damage in late age would result in lowered glomerulosclerosis, we administered the mitochondrial targeted peptide, SS-31, to aged mice...
January 4, 2017: Kidney International
https://www.readbyqxmd.com/read/28059052/gastrin-enhances-autophagy-and-promotes-gastric-carcinoma-proliferation-via-inducing-ampk%C3%AE
#7
Zhuang Kun, Guo Hanqing, Tang Hailing, Yan Yuan, Zhang Jun, Zhang Lingxia, Han Kun, Zhang Xin
Gastric cancer (GC) is one of the most frequent epithelial malignancies worldwide. The gastrointestinal (GI) peptide gastrin is an important regulator of the secretion and release of gastric acid from stomach parietal cells and it also plays a vital role in the development and progression of gastric cancer. The aim of the current study was to investigate the role and underlying mechanism of gastrin and autophagy in regulating gastric cancer tumorigenesis. Gastrin-17 amide (G-17) was applied in the gastric cancer cell lines SGC7901 and MGC-803...
January 5, 2017: Oncology Research
https://www.readbyqxmd.com/read/28052057/wnt-%C3%AE-catenin-promotes-gastric-fundus-specification-in-mice-and-humans
#8
Kyle W McCracken, Eitaro Aihara, Baptiste Martin, Calyn M Crawford, Taylor Broda, Julie Treguier, Xinghao Zhang, John M Shannon, Marshall H Montrose, James M Wells
Despite the global prevalence of gastric disease, there are few adequate models in which to study the fundus epithelium of the human stomach. We differentiated human pluripotent stem cells (hPSCs) into gastric organoids containing fundic epithelium by first identifying and then recapitulating key events in embryonic fundus development. We found that disruption of Wnt/β-catenin signalling in mouse embryos led to conversion of fundic to antral epithelium, and that β-catenin activation in hPSC-derived foregut progenitors promoted the development of human fundic-type gastric organoids (hFGOs)...
January 12, 2017: Nature
https://www.readbyqxmd.com/read/28012457/identification-of-novel-genetic-markers-for-mouse-yolk-sac-cells-by-using-microarray-analyses
#9
Shinomi Yagi, Nobuyoshi Shiojiri
The mouse embryonic yolk sac consists of a visceral yolk sac (VYS) and parietal yolk sac (PYS), and may function as a materno-fetal exchange system for nutrients and wastes, and physical protector for the embryo/fetus. The present study was undertaken to characterize gene expression of the VYS and PYS endodermal cells, and to identify their novel genetic markers from microarray data. Apoa4, Lrp2, Fxyd2, Slc34a3 and Entpd2 were predominantly expressed in VYS epithelial cells. Gkn2 and Pga5 were selected as markers for PYS cells...
January 2017: Placenta
https://www.readbyqxmd.com/read/27998643/activated-erk1-2-increases-cd44-in-glomerular-parietal-epithelial-cells-leading-to-matrix-expansion
#10
Sebastian S Roeder, Taylor J Barnes, Jonathan S Lee, India Kato, Diana G Eng, Natalya V Kaverina, Maria W Sunseri, Christoph Daniel, Kerstin Amann, Jeffrey W Pippin, Stuart J Shankland
The glycoprotein CD44 is barely detected in normal mouse and human glomeruli, but is increased in glomerular parietal epithelial cells following podocyte injury in focal segmental glomerulosclerosis (FSGS). To determine the biological role and regulation of CD44 in these cells, we employed an in vivo and in vitro approach. Experimental FSGS was induced in CD44 knockout and wild-type mice with a cytotoxic podocyte antibody. Albuminuria, focal and global glomerulosclerosis (periodic acid-Schiff stain), and collagen IV staining were lower in CD44 knockout compared with wild-type mice with FSGS...
April 2017: Kidney International
https://www.readbyqxmd.com/read/27990460/the-development-of-spasmolytic-polypeptide-tff2-expressing-metaplasia-spem-during-gastric-repair-is-absent-in-the-aged-stomach
#11
Amy C Engevik, Rui Feng, Eunyoung Choi, Shana White, Nina Bertaux-Skeirik, Jing Li, Maxime M Mahe, Eitaro Aihara, Li Yang, Betsy DiPasquale, Sunghee Oh, Kristen A Engevik, Andrew S Giraud, Marshall H Montrose, Mario Medvedovic, Michael A Helmrath, James R Goldenring, Yana Zavros
BACKGROUND & AIMS: During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2-expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27920570/formation-of-tight-junctions-between-neighboring-podocytes-is-an-early-ultrastructural-feature-in-experimental-crescentic-glomerulonephritis
#12
Lena Succar, Ross A Boadle, David C Harris, Gopala K Rangan
PURPOSE: In crescentic glomerulonephritis (CGN), the development of cellular bridges between podocytes and parietal epithelial cells (PECs) triggers glomerular crescent formation. However, the sequential changes in glomerular ultrastructure in CGN are not well defined. This study investigated the time course of glomerular ultrastructure in experimental CGN. METHODS: Transmission electron microscopy (TEM) was performed using kidney samples from rats with nephrotoxic serum nephritis (NSN) from day 1 to day 14...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27917461/intussusceptive-angiogenesis-and-expression-of-tie-receptors-during-porcine-metanephric-kidney-development
#13
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...
December 5, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27895155/investigations-of-glucocorticoid-action-in-gn
#14
Christoph Kuppe, Claudia van Roeyen, Katja Leuchtle, Nazanin Kabgani, Michael Vogt, Marc Van Zandvoort, Bart Smeets, Jürgen Floege, Hermann-Josef Gröne, Marcus J Moeller
For several decades, glucocorticoids have been used empirically to treat rapid progressive GN. It is commonly assumed that glucocorticoids act primarily by dampening the immune response, but the mechanisms remain incompletely understood. In this study, we inactivated the glucocorticoid receptor (GR) specifically in kidney epithelial cells using Pax8-Cre/GR(fl/fl) mice. Pax8-Cre/GR(fl/fl) mice did not exhibit an overt spontaneous phenotype. In mice treated with nephrotoxic serum to induce crescentic nephritis (rapidly progressive GN), this genetic inactivation of the GR in kidney epithelial cells exerted renal benefits, including inhibition of albuminuria and cellular crescent formation, similar to the renal benefits observed with high-dose prednisolone in control mice...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27873093/fatty-acids-in-a-high-fat-diet-potentially-induce-gastric-parietal-cell-damage-and-metaplasia-in-mice
#15
Yuki Hirata, Takuhito Sezaki, Miwa Tamura-Nakano, Chinatsu Oyama, Teruki Hagiwara, Takamasa Ishikawa, Shinji Fukuda, Kazuhiko Yamada, Kazuhide Higuchi, Taeko Dohi, Yuki I Kawamura
BACKGROUND: Obesity is associated with risk of adenocarcinoma in the proximal stomach. We aimed to identify the links between dietary fat and gastric premalignant lesions. METHODS: C57BL/6 mice were fed high fat diet (HFD), and gastric mucosa was histologically analysed. Morphological changes were also analysed using an electron microscope. Transcriptome analysis of purified parietal cells was performed, and non-parietal gastric corpus epithelial cells were subjected to single-cell gene-expression profiling...
November 21, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27852932/epididymis-like-tubules-in-adult-renal-hypodysplasia-immunohistochemical-features-indicate-a-mesonephric-origin
#16
Madhavi A Naik, Sanjay A Pai
We report the presence of epididymis-like tubules in unilateral renal hypodysplasia in 3 adult men. Microscopy showed dilated tubules lined by ciliated columnar epithelium and smaller basal cells, morphologically resembling epididymal tubules. Small tubules lined by cuboidal epithelium were also present in all cases, with glomeruli in 2 cases. The epididymis-like tubules expressed CD10, CK7, PAX8, and AR in the luminal epithelium, while the basal cells were positive for p63, CK7, and focally for CD10. The smooth muscle bundles around the epididymis-like tubules were focally AR and WT1 (cytoplasmic) positive...
November 16, 2016: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27766298/epithelial-regeneration-after-gastric-ulceration-causes-prolonged-cell-type-alterations
#17
Eitaro Aihara, Andrea L Matthis, Rebekah A Karns, Kristen A Engevik, Peihua Jiang, Jiang Wang, Bruce R Yacyshyn, Marshall H Montrose
BACKGROUND & AIMS: The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases. METHODS: Gastric ulcers were induced in mice by serosal topical application of acetic acid...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27756386/helicobacter-suis-affects-the-health-and-function-of-porcine-gastric-parietal-cells
#18
Guangzhi Zhang, Richard Ducatelle, Belgacem Mihi, Annemieke Smet, Bram Flahou, Freddy Haesebrouck
The stomach of pigs at slaughter age is often colonized by Helicobacter (H.) suis, which is also the most prevalent gastric non-H. pylori Helicobacter (NHPH) species in humans. It is associated with chronic gastritis, gastric ulceration and other gastric pathological changes in both hosts. Parietal cells are highly specialized, terminally differentiated epithelial cells responsible for gastric acid secretion and regulation. Dysfunction of these cells is closely associated with gastric pathology and disease...
October 19, 2016: Veterinary Research
https://www.readbyqxmd.com/read/27750091/hedgehog-signaling-in-the-stomach
#19
REVIEW
Daniel Konstantinou, Nina Bertaux-Skeirik, Yana Zavros
The Hedgehog (Hh) signaling pathway not only plays a key part in controlling embryonic development, but in the adult stomach governs important cellular events such as epithelial cell differentiation, proliferation, gastric disease, and regeneration. In particular, Sonic Hedgehog (Shh) signaling has been well studied for its role in gastric physiology and pathophysiology. Shh is secreted from the gastric parietal cells and contributes to the regeneration of the epithelium in response to injury, or the development of gastritis during Helicobacter pylori infection...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27744657/pathogenesis-of-focal-segmental-glomerulosclerosis
#20
REVIEW
Beom Jin Lim, Jae Won Yang, Woo Sung Do, Agnes B Fogo
Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS...
November 2016: Journal of Pathology and Translational Medicine
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