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https://www.readbyqxmd.com/read/28331448/antibody-mediated-rejection-a-review
#1
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J Cohen, George E Loss
BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28320530/single-cell-rna-sequence-analysis-of-mouse-glomerular-mesangial-cells-uncovers-mesangial-cell-essential-genes
#2
Yuqiu Lu, Yuting Ye, Qianqian Yang, Shaolin Shi
Mesangial cells are essential for the structure and function of glomeruli, but the mechanisms underlying these roles are not well understood. Here, we performed a single-cell RNA-sequence (RNA-seq) analysis of mouse mesangial cells using the Fluidigm C1 platform. We found that gene expression in individual mesangial cells was tremendously heterogeneous, with mean correlation coefficients of 0.20, and most mesangial genes were actually expressed in only a portion of mesangial cells and are therefore presumably dispensable...
March 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28289183/c1-inhibitor-decreases-the-release-of-vasculitis-like-chemotactic-endothelial-microvesicles
#3
Maria Mossberg, Anne-Lie Ståhl, Robin Kahn, Ann-Charlotte Kristoffersson, Ramesh Tati, Caroline Heijl, Mårten Segelmark, L M Fredrik Leeb-Lundberg, Diana Karpman
The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0...
March 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28288344/stereological-and-immunogold-studies-on-tie1-and-tie2-localization-in-glomeruli-indicate-angiopoietin-signaling-in-podocytes
#4
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...
March 2, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28266128/ablation-of-endothelial-prolyl-hydroxylase-domain-protein-2-promotes-renal-vascular-remodelling-and-fibrosis-in-mice
#5
Shuo Wang, Heng Zeng, Sean T Chen, Liying Zhou, Xue-Jiao Xie, Xiaochen He, Yong-Kang Tao, Qin-Hui Tuo, Changqin Deng, Duan-Fang Liao, Jian-Xiong Chen
Accumulating evidence demonstrates that hypoxia-inducible factor (HIF-α) hydroxylase system has a critical role in vascular remodelling. Using an endothelial-specific prolyl hydroxylase domain protein-2 (PHD2) knockout (PHD2(EC) KO) mouse model, this study investigates the regulatory role of endothelial HIF-α hydroxylase system in the development of renal fibrosis. Knockout of PHD2 in EC up-regulated the expression of HIF-1α and HIF-2α, resulting in a significant decline of renal function as evidenced by elevated levels of serum creatinine...
March 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28254368/the-impact-of-tumor-biology-on-survival-and-response-to-radiation-therapy-among-patients-with-non-small-cell-lung-cancer-brain-metastases
#6
Jacob A Miller, Rupesh Kotecha, Manmeet S Ahluwalia, Alireza M Mohammadi, John H Suh, Gene H Barnett, Erin S Murphy, Michael A Vogelbaum, Lilyana Angelov, Samuel T Chao
PURPOSE: To investigate the natural history and response to radiation therapy among ALK-rearranged, EGFR-mutated, wild-type adenocarcinoma, and squamous cell non-small cell lung cancer (NSCLC) brain metastases. METHODS AND MATERIALS: Patients with NSCLC brain metastasis diagnosed from 1989 through 2014 at a single tertiary-care institution were included. The primary outcome was overall survival, whereas secondary outcomes included local failure, distant intracranial failure, and radiation necrosis...
January 5, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28239987/effects-of-alloantibodies-to-human-leukocyte-antigen-on-endothelial-expression-and-serum-levels-of-thrombomodulin
#7
S Béland, P Vallin, O Désy, E Lévesque, S A De Serres
Essentials The effect of alloantibodies on the endothelial expression of thrombomodulin is unknown. Thrombomodulin was quantified in stimulated endothelial cells and measured in serum samples. Anti-human leukocyte antigen (HLA) I vs. II antibodies have different effects on thrombomodulin. Anti-HLA II antibodies may promote a prothrombotic state and contribute to microangiopathy. SUMMARY: Rationale Thrombomodulin (TBM) is an anticoagulant and anti-inflammatory transmembrane protein expressed on endothelial cells...
February 26, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28237245/the-formation-of-quiescent-glomerular-endothelial-cell-monolayer-in-vitro-is-strongly-dependent-on-the-choice-of-extracellular-matrix-coating
#8
Kamilla Pajęcka, Malik Nygaard Nielsen, Troels Krarup Hansen, Julie M Williams
BACKGROUND AND AIMS: Nephropathy involves pathophysiological changes to the glomerulus. The primary glomerular endothelial cells (GEnCs) have emerged as an important tool for studying glomerulosclerotic mechanisms and in the screening process for drug-candidates. The success of the studies is dependent on the quality of the cell model. Therefore, we set out to establish an easy, reproducible model of the quiescent endothelial monolayer with the use of commercially available extracellular matrices (ECMs)...
February 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28228399/accumulation-of-worn-out-gbm-material-substantially-contributes-to-mesangial-matrix-expansion-in-diabetic-nephropathy
#9
Wilhelm Kriz, Jana Löwen, Giuseppina Federico, Jacob van den Born, Elisabeth Gröne, Hermann-Josef Gröne
Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of diabetic nephropathy (DN) generally considered to emerge from different sites of overproduction; GBM components from podocytes and mesangial matrix from mesangial cells. Re-evaluation of 918 biopsies with DN revealed strong evidence that these mechanisms are connected to each other, wherein excess GBM components fail to undergo degradation and are deposited in the mesangium. These data do not exclude that also mesangial cells synthesize components that contribute to the accumulation of matrix in the mesangium...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28183278/a-rare-case-of-renal-thrombotic-microangiopathy-associated-with-castleman-s-disease
#10
Anubha Mutneja, L Nicholas Cossey, Helen Liapis, Ying Maggie Chen
BACKGROUND: Castleman's disease (CD) is an uncommon, heterogeneous lympho-proliferative disorder leading to high circulating levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). Renal involvement has been only described in a limited number of small studies. Herein, we report a rare case of renal thrombotic microangiopathy (TMA) associated with CD and investigate the podocyte expression of VEGF in the renal biopsy prior to initiation of treatment. CASE PRESENTATION: An 18-year-old male presented with fever, diarrhea, diffuse lymphadenopathy, ascites and acute kidney injury...
February 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28181422/hmgb1-contributes-to-glomerular-endothelial-cell-injury-in-anca-associated-vasculitis-through-enhancing-endothelium-neutrophil-interactions
#11
Chen Wang, Dong-Yuan Chang, Min Chen, Ming-Hui Zhao
Our previous studies demonstrated that high mobility group box-1 (HMGB1), a typical damage-associated molecular pattern (DAMP) protein, is associated with the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Moreover, HMGB1 participates in ANCA-induced neutrophil activation. The current study aimed to investigate whether HMGB1 regulated the interaction between neutrophils and glomerular endothelial cells (GEnC) in the presence of ANCA. Correlation analysis on HMGB1 levels in AAV patients and soluble intercellular cell adhesion molecule-1 (sICAM-1) levels or vascular endothelial growth factor (VEGF) levels, which are markers of endothelial cell activation, was performed...
February 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28164557/the-detection-of-urinary-podocytes-from-drug-induced-glomerular-thrombotic-microangiopathy-in-advanced-cancer-patients
#12
Joichi Usui, Chie Yokoyama, Masahiro Hagiwara, Kai Hirayasu, Takahiro Kojima, Takayuki Yoshino, Hiroyuki Nishiyama, Masanori Hara, Kunihiro Yamagata
BACKGROUND: Focusing on glomerular thrombotic microangiopathy (TMA), we detected urinary podocytes to evaluate podocyte damage following glomerular endothelial cell injury. METHODS: We analyzed the relationship between urinary podocytes as biomarkers for podocyte injuries and clinical manifestations in five patients of anti-cancer-drug-induced glomerular TMA. RESULTS: Cancer in all five patients was advanced, including 4 cases of renal cell carcinoma treated with tyrosine kinase inhibitor, and one with intrahepatic bile duct carcinoma treated with gemcitabine...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28148530/usp40-gene-knockdown-disrupts-glomerular-permeability-in-zebrafish
#13
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...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28139439/neutrophil-protease-cleavage-of-von-willebrand-factor-in-glomeruli-an-anti-thrombotic-mechanism-in-the-kidney
#14
Ramesh Tati, Ann-Charlotte Kristoffersson, Minola Manea Hedström, Matthias Mörgelin, Jörgen Wieslander, Cees van Kooten, Diana Karpman
Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28137583/nod2-promotes-endothelial-to-mesenchymal-transition-of-glomerular-endothelial-cells-via-mek-erk-signaling-pathway-in-diabetic-nephropathy
#15
Jin Shang, Ya Zhang, Yumin Jiang, Zhenzhen Li, Yiqi Duan, Luyao Wang, Jing Xiao, Zhanzheng Zhao
Endothelial-to-mesenchymal transition (EndMT) of glomerular vascular endothelial cells (GEnCs) is now considered to play a critical role in diabetic nephropathy (DN). NOD2 is newly discovered to be closely related to DN renal injury. However, the relationship between NOD2 and EndMT of GEnCs has never been reported. In the present study, we found that NOD2 over-expression was positively correlated with the severity of DN injury in human renal biopsy samples. Immunohistochemical staining of DN renal slices showed gradual absence of endothelial character and gain of mesenchymal character, both of which were associated with NOD2 over-expression...
January 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28112392/intracellular-transcytosis-of-albumin-in-glomerular-endothelial-cells-after-endocytosis-through-caveolae
#16
Takahito Moriyama, Kayo Sasaki, Kazunori Karasawa, Keiko Uchida, Kosaku Nitta
BACKGROUND/AIMS: We previously described albumin endocytosis through caveolae in human renal glomerular endothelial cells (HRGECs). This suggested a new albumin transcytosis pathway, in addition to the fenestral pathway. As a next step, we investigated albumin transcytosis in HRGECs after caveolar endocytosis. METHODS AND RESULTS: HRGECs were incubated with Alexa Fluor 488-labeled bovine serum albumin from 0 to 360 minutes. Next, markers for endosomes, endoplasmic reticulum (ER), golgi apparatus (GA), lysosomes and proteasomes and Fc receptors, microtubules and actin were monitored by immunofluorescence...
January 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28101903/development-and-characterization-of-anti-glycopeptide-monoclonal-antibodies-against-human-podoplanin-using-glycan-deficient-cell-lines-generated-by-crispr-cas9-and-talen
#17
Mika K Kaneko, Takuro Nakamura, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Shinji Abe, Michiaki Takagi, Hiroyuki Harada, Hiroyoshi Suzuki, Yasuhiko Nishioka, Yukinari Kato
Human podoplanin (hPDPN), which binds to C-type lectin-like receptor-2 (CLEC-2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer-associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung-type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mAbs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti-hPDPN mAb, LpMab-21...
February 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28081450/heparanase-driven-inflammation-from-the-ages-stimulated-macrophages-changes-the-functions-of-glomerular-endothelial-cells
#18
Guang Xu, Qiaojing Qin, Min Yang, Zhongdong Qiao, Yong Gu, Jianying Niu
AIMS: Amounts of macrophages were infiltrated in glomeruli in diabetic nephropathy. Heparanase has been thought to be closely related to proteinuria. Our aims were to determine the effect of heparanase on the inflammation in AGEs-stimulated macrophages and its role on the functions of glomerular endothelial cells (GEnCs). METHODS: The expression of inflammation cytokines in macrophages were assayed by q-RT PCR, western, and ELISA. Then western was used to measure the expression of RAGE and key proteins in NF-κB pathway in macrophages...
February 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28078995/sphingolipids-in-genetic-and-acquired-forms-of-chronic-kidney-diseases
#19
Norishi Ueda
Sphingolipids (SLs) regulate apoptosis, proliferation, and stress response. SLs, including ceramide, glycosphingolipids (glucosylceramide, lactosylceramide, and gangliosides) and sphingosine-1-phosphate (S1P), play a role in the pathogenesis and progression of genetic (lysosomal storage disease, congenital nephrotic syndrome and polycystic kidney disease) and non-genetic forms of chronic kidney diseases (CKDs). SLs metabolism defects promote complications (cardiovascular events, etc.) via oxidant stress in CKDs...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28072729/hypertonic-saline-protects-brain-endothelial-cells-against-hypoxia-correlated-to-the-levels-of-estimated-glomerular-filtration-rate-and-interleukin-1%C3%AE
#20
Sheng-Long Chen, Yi-Yu Deng, Qiao-Sheng Wang, Yong-Li Han, Wen-Qiang Jiang, Ming Fang, Bei Hu, Zhi-Xin Wu, Lin-Qiang Huang, Hong-Ke Zeng
OBJECTIVE: The aim of this study was to verify the protective effect of hypertonic saline (HS) on brain endothelial cells under hypoxic conditions and the relevant underlying mechanism. METHODS: bEnd.3 cells were treated with oxygen-glucose deprivation (OGD)-induced injury. To measure HS performance, cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt assay, and cell apoptosis was assessed by flow cytometry and Terminal deoxynucleotidyl transferase UTP nick-end labeling staining...
January 2017: Medicine (Baltimore)
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