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1,603 results on '"van Kuppevelt, Toin H"'

3. Publisher Correction: Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation

Author

Patel, Vaishali N., Aure, Marit H., Choi, Sophie H., Ball, James R., Lane, Ethan D., Wang, Zhangjie, Xu, Yongmei, Zheng, Changyu, Liu, Xibao, Martin, Daniel, Pailin, Jillian Y., Prochazkova, Michaela, Kulkarni, Ashok B., van Kuppevelt, Toin H., Ambudkar, Indu S., Liu, Jian, and Hoffman, Matthew P.

Published
2024
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7. Peroxisome proliferator-activated receptor ɣ agonist mediated inhibition of heparanase expression reduces proteinuria

Author

Garsen, Marjolein, Buijsers, Baranca, Sol, Marloes, Gockeln, Lena, Sonneveld, Ramon, van Kuppevelt, Toin H., de Graaf, Mark, van den Born, Jacob, Kamps, Jan A.A.M., van Raalte, Daniël H., van der Meer, Rutger W., Lamb, Hildo J., Hillebrands, Jan-Luuk, Rabelink, Ton J., Maciej-Hulme, Marissa L., Krenning, Guido, Nijenhuis, Tom, and van der Vlag, Johan

Published
2023
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10. A mutant-cell library for systematic analysis of heparan sulfate structure–function relationships

Author

Qiu, Hong, Shi, Songshan, Yue, Jingwen, Xin, Meng, Nairn, Alison V, Lin, Lei, Liu, Xinyue, Li, Guoyun, Archer-Hartmann, Stephanie A, Dela Rosa, Mitche, Galizzi, Melina, Wang, Shunchun, Zhang, Fuming, Azadi, Parastoo, van Kuppevelt, Toin H, Cardoso, Wellington V, Kimata, Koji, Ai, Xingbin, Moremen, Kelley W, Esko, Jeffrey D, Linhardt, Robert J, and Wang, Lianchun

Subjects
Biochemistry and Cell Biology, Biological Sciences, 2.1 Biological and endogenous factors, Animals, Antibodies, Antibody Specificity, Cells, Cultured, Endothelium, Vascular, Epitopes, Heparitin Sulfate, Lung, Mice, Inbred C57BL, Mutation, Peptide Library, Signal Transduction, Structure-Activity Relationship, Sulfur, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

Heparan sulfate (HS) is a complex linear polysaccharide that modulates a wide range of biological functions. Elucidating the structure-function relationship of HS has been challenging. Here we report the generation of an HS-mutant mouse lung endothelial cell library by systematic deletion of HS genes expressed in the cell. We used this library to (1) determine that the strictly defined fine structure of HS, not its overall degree of sulfation, is more important for FGF2-FGFR1 signaling; (2) define the epitope features of commonly used anti-HS phage display antibodies; and (3) delineate the fine inter-regulation networks by which HS genes modify HS and chain length in mammalian cells at a cell-type-specific level. Our mutant-cell library will allow robust and systematic interrogation of the roles and related structures of HS in a cellular context.

Published
2018

12. Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin α2 as a Host Factor for Bacterial Invasion

Author

van Wijk, Xander M, Döhrmann, Simon, Hallström, Björn M, Li, Shangzhong, Voldborg, Bjørn G, Meng, Brandon X, McKee, Karen K, van Kuppevelt, Toin H, Yurchenco, Peter D, Palsson, Bernhard O, Lewis, Nathan E, Nizet, Victor, and Esko, Jeffrey D

Subjects
Microbiology, Biological Sciences, Biomedical and Clinical Sciences, Infectious Diseases, Emerging Infectious Diseases, Genetics, Biotechnology, Human Genome, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection, Animals, CHO Cells, Cricetinae, Cricetulus, Endocytosis, Gene Deletion, Gene Knockout Techniques, Genetic Complementation Test, Host-Pathogen Interactions, Laminin, Sequence Analysis, DNA, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Biochemistry and cell biology, Medical microbiology
Abstract

To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-cas9) gene targeting. When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A Streptococcus, and Staphylococcus aureus was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-cas9 mutants were only resistant to GBS. Invasion of pgsA745 cells was not restored by transfection with xylosyltransferase, suggesting that an additional mutation conferring panresistance to multiple bacteria was present in pgsA745 cells. Whole-genome sequencing and transcriptome sequencing (RNA-Seq) uncovered a deletion in the gene encoding the laminin subunit α2 (Lama2) that eliminated much of domain L4a. Silencing of the long Lama2 isoform in wild-type cells strongly reduced bacterial invasion, whereas transfection with human LAMA2 cDNA significantly enhanced invasion in pgsA745 cells. The addition of exogenous laminin-α2β1γ1/laminin-α2β2γ1 strongly increased bacterial invasion in CHO cells, as well as in human alveolar basal epithelial and human brain microvascular endothelial cells. Thus, the L4a domain in laminin α2 is important for cellular invasion by a number of bacterial pathogens.ImportancePathogenic bacteria penetrate host cellular barriers by attachment to extracellular matrix molecules, such as proteoglycans, laminins, and collagens, leading to invasion of epithelial and endothelial cells. Here, we show that cellular invasion by the human pathogens group B Streptococcus, group A Streptococcus, and Staphylococcus aureus depends on a specific domain of the laminin α2 subunit. This finding may provide new leads for the molecular pathogenesis of these bacteria and the development of novel antimicrobial drugs.

Published
2017

20. Modulation of heparan sulfate in the glomerular endothelial glycocalyx decreases leukocyte influx during experimental glomerulonephritis.

Author

Rops, Angelique LWMM, Loeven, Markus A, van Gemst, Jasper J, Eversen, Iris, Van Wijk, Xander M, Dijkman, Henry B, van Kuppevelt, Toin H, Berden, Jo HM, Rabelink, Ton J, Esko, Jeffrey D, and van der Vlag, Johan

Subjects
Kidney Glomerulus, Leukocytes, Cell Line, Glycocalyx, Endothelial Cells, Animals, Mice, Inbred C57BL, Mice, Knockout, Anti-Glomerular Basement Membrane Disease, Disease Models, Animal, Sulfotransferases, Heparitin Sulfate, L-Selectin, Chemokines, Autoantibodies, Coculture Techniques, Transfection, Cell Adhesion, Signal Transduction, Chemotaxis, Leukocyte, Down-Regulation, RNA Interference, Time Factors, Female, Male, acute kidney injury, anti-GBM disease, endothelium, glomerular endothelial cells, glomerular filtration barrier, glomerulonephritis, glycocalyx, heparan sulfate, Mice, Inbred C57BL, Knockout, Disease Models, Animal, Chemotaxis, Leukocyte, Clinical Sciences, Urology & Nephrology
Abstract

The glomerular endothelial glycocalyx is postulated to be an important modulator of permeability and inflammation. The glycocalyx consists of complex polysaccharides, the main functional constituent of which, heparan sulfate (HS), is synthesized and modified by multiple enzymes. The N-deacetylase-N-sulfotransferase (Ndst) enzymes initiate and dictate the modification process. Here we evaluated the effects of modulation of HS in the endothelial glycocalyx on albuminuria and glomerular leukocyte influx using mice deficient in endothelial and leukocyte Ndst1 (TEKCre+/Ndst1flox/flox). In these mice, glomerular expression of a specific HS domain was significantly decreased, whereas the expression of other HS domains was normal. In the endothelial glycocalyx, this specific HS structure was not associated with albuminuria or with changes in renal function. However, glomerular leukocyte influx was significantly reduced during antiglomerular basement membrane nephritis, which was associated with less glomerular injury and better renal function. In vitro decreased adhesion of wild-type and Ndst1-deficient granulocytes to Ndst1-silenced glomerular endothelial cells was found, accompanied by a decreased binding of chemokines and L-selectin. Thus, modulation of HS in the glomerular endothelial glycocalyx significantly reduced the inflammatory response in antiglomerular basement membrane nephritis.

Published
2014

23. Podocyte-specific deletion of NDST1, a key enzyme in the sulfation of heparan sulfate glycosaminoglycans, leads to abnormalities in podocyte organization in vivo.

Author

Sugar, Terrel, Wassenhove-McCarthy, Deborah J, Esko, Jeffrey D, van Kuppevelt, Toin H, Holzman, Lawrence, and McCarthy, Kevin J

Subjects
Animals, Mice, Knockout, Mice, Albuminuria, Hypertrophy, Disease Progression, Sulfotransferases, Agrin, Cell Proliferation, Genotype, Phenotype, Time Factors, Female, Male, Podocytes, Heparan Sulfate Proteoglycans, cell-matrix adhesion, extracellular matrix, glycosaminoglycan, heparan, podocyte, proteoglycan, Knockout, Clinical Sciences, Urology & Nephrology
Abstract

Heparan sulfate proteoglycans have been shown to modulate podocyte adhesion to--and pedicel organization on--the glomerular basement membrane. Recent studies showed that foot process effacement developed in a mutant mouse model whose podocytes were unable to assemble heparan sulfate glycosaminoglycan chains. This study, a further refinement, explored the role of heparan N-sulfation on podocyte behavior. A novel mutant mouse (Ndst1(-/-)) was developed, having podocyte-specific deletion of Ndst1, the enzyme responsible for N-sulfation of heparan sulfate chains. Podocytes having this mutation had foot process effacement and abnormal adhesion to Bowman's capsule. Although glomerular hypertrophy did develop in the kidneys of mutant animals, mesangial expansion was not seen. The lack of heparan N-sulfation did not affect the expression of agrin or perlecan proteoglycan core proteins. Loss of N-sulfation did not result in significant proteinuria, but the increase in the albumin/creatinine ratio was coincident with the development of the enlarged lysosomes in the proximal tubules. Thus, although the renal phenotype of the Ndst1(-/-) mouse is mild, the data show that heparan chain N-sulfation plays a key role in podocyte organization.

Published
2014

43. Supplementary Methods from Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

Author

Thelin, Martin A., primary, Svensson, Katrin J., primary, Shi, Xiaofeng, primary, Bagher, Mariam, primary, Axelsson, Jakob, primary, Isinger-Ekstrand, Anna, primary, van Kuppevelt, Toin H., primary, Johansson, Jan, primary, Nilbert, Mef, primary, Zaia, Joseph, primary, Belting, Mattias, primary, Maccarana, Marco, primary, and Malmström, Anders, primary

Published
2023
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44. Data from Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

Author

Thelin, Martin A., primary, Svensson, Katrin J., primary, Shi, Xiaofeng, primary, Bagher, Mariam, primary, Axelsson, Jakob, primary, Isinger-Ekstrand, Anna, primary, van Kuppevelt, Toin H., primary, Johansson, Jan, primary, Nilbert, Mef, primary, Zaia, Joseph, primary, Belting, Mattias, primary, Maccarana, Marco, primary, and Malmström, Anders, primary

Published
2023
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45. Supplementary Table 1 from Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

Author

Thelin, Martin A., primary, Svensson, Katrin J., primary, Shi, Xiaofeng, primary, Bagher, Mariam, primary, Axelsson, Jakob, primary, Isinger-Ekstrand, Anna, primary, van Kuppevelt, Toin H., primary, Johansson, Jan, primary, Nilbert, Mef, primary, Zaia, Joseph, primary, Belting, Mattias, primary, Maccarana, Marco, primary, and Malmström, Anders, primary

Published
2023
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46. Supplementary Table 2 from Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

Author

Thelin, Martin A., primary, Svensson, Katrin J., primary, Shi, Xiaofeng, primary, Bagher, Mariam, primary, Axelsson, Jakob, primary, Isinger-Ekstrand, Anna, primary, van Kuppevelt, Toin H., primary, Johansson, Jan, primary, Nilbert, Mef, primary, Zaia, Joseph, primary, Belting, Mattias, primary, Maccarana, Marco, primary, and Malmström, Anders, primary

Published
2023
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47. Supplementary Figures 1-3 from Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

Author

Thelin, Martin A., primary, Svensson, Katrin J., primary, Shi, Xiaofeng, primary, Bagher, Mariam, primary, Axelsson, Jakob, primary, Isinger-Ekstrand, Anna, primary, van Kuppevelt, Toin H., primary, Johansson, Jan, primary, Nilbert, Mef, primary, Zaia, Joseph, primary, Belting, Mattias, primary, Maccarana, Marco, primary, and Malmström, Anders, primary

Published
2023
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