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Heparanase

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https://www.readbyqxmd.com/read/28103268/direct-observation-of-enhanced-nitric-oxide-in-a-murine-model-of-diabetic-nephropathy
#1
Margien G S Boels, Ernst E H van Faassen, M Cristina Avramut, Johan van der Vlag, Bernard M van den Berg, Ton J Rabelink
Uncoupling of nitric oxide synthase (NOS) secondary to redox signaling is a central mechanism in endothelial and macrophage activation. To date studies on the production of nitric oxide (NO) during the development of diabetic complications show paradoxical results. We previously showed that recoupling eNOS by increasing the eNOS cofactor tetrahydrobiopterin (BH4) could restore endothelial function and prevent kidney injury in experimental kidney transplantation. Here, we employed a diabetic mouse model to investigate the effects of diabetes on renal tissue NO bioavailability...
2017: PloS One
https://www.readbyqxmd.com/read/28081450/heparanase-driven-inflammation-from-the-ages-stimulated-macrophages-changes-the-functions-of-glomerular-endothelial-cells
#2
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...
December 30, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28075546/matrix-pathobiology-central-roles-for-proteoglycans-and-heparanase-in-health-and-disease
#3
Nikos K Karamanos
This thematic minireview series highlights new concepts in matrix pathobiology. The reviews in this series cover the roles of the two matrix proteoglycans, decorin and biglycan, in inflammation and autophagy, the various functions of syndecans in cancer development and prognosis and the recently discovered mechanisms underlying the multiple roles of heparanase in cancer progression, inflammation, and autophagy.
January 2017: FEBS Journal
https://www.readbyqxmd.com/read/28064160/specific-heparanase-inhibition-reverses-glucose-induced-mesothelial-to-mesenchymal-transition
#4
Valentina Masola, Simona Granata, Gloria Bellin, Giovanni Gambaro, Maurizio Onisto, Carlo Rugiu, Antonio Lupo, Gianluigi Zaza
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells induced by high glucose (HG) levels is a major biological mechanism leading to myofibroblast accumulation in the omentum of patients on peritoneal dialysis (PD). Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate chains, is involved in the EMT of several cell lines, and may have a major role in this pro-fibrotic process potentially responsible for the failure of dialysis. Its specific inhibition may therefore plausibly minimize this pathological condition...
January 7, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28038446/heparanase-augments-insulin-receptor-signaling-in-breast-carcinoma
#5
Rachel Goldberg, Amir Sonnenblick, Esther Hermano, Tamar Hamburger, Amichay Meirovitz, Tamar Peretz, Michael Elkin
Recently, growing interest in the potential link between metabolic disorders (i.e., diabetes, obesity, metabolic syndrome) and breast cancer has mounted, including studies which indicate that diabetic/hyperinsulinemic women have a significantly higher risk of bearing breast tumors that are more aggressive and associated with higher death rates. Insulin signaling is regarded as a major contributor to this phenomenon; much less is known about the role of heparan sulfate-degrading enzyme heparanase in the link between metabolic disorders and cancer...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025251/non-reducing-end-labeling-of-heparan-sulfate-via-click-chemistry-and-a-high-throughput-elisa-assay-for-heparanase
#6
Zhengliang L Wu, Xinyi Huang, Cheryl Ethen, Timothy Tatge, Marta Pasek, Joseph Zaia
Heparan sulfate (HS) is a linear polysaccharide found in the extracellular matrix (ECM) and on the cell membrane. It plays numerous roles in cellular events, including cell growth, migration and differentiation through binding to various growth factors, cytokines and other ECM proteins. Heparanase (HPSE) is an endoglycosidase that cleaves HS in the ECM and cell membrane. By degrading HS, HPSE not only alters the integrity of the ECM but also releases growth factors and angiogenic factors bound to HS chains, therefore, changes various cellular activities, including cell mobility that is critical for cancer metastasis...
December 26, 2016: Glycobiology
https://www.readbyqxmd.com/read/27999107/heparanase-overexpression-induces-glucagon-resistance-and-protects-animals-from-chemically-induced-diabetes
#7
Dahai Zhang, Fulong Wang, Nathaniel Lal, Amy Pei-Ling Chiu, Andrea Wan, Jocelyn Jia, Denise Bierende, Stephane Flibotte, Sunita Sinha, Ali Asadi, Xiaoke Hu, Farnaz Taghizadeh, Thomas Pulinilkunnil, Corey Nislow, Israel Vlodavsky, James D Johnson, Timothy J Kieffer, Bahira Hussein, Brian Rodrigues
Heparanase, a protein with enzymatic and nonenzymatic properties, contributes toward disease progression and prevention. In the current study, a fortuitous observation in transgenic mice globally overexpressing heparanase (hep-tg) was the discovery of improved glucose homeostasis. We examined the mechanisms that contribute toward this improved glucose metabolism. Heparanase overexpression was associated with enhanced glucose-stimulated insulin secretion and hyperglucagonemia, in addition to changes in islet composition and structure...
January 2017: Diabetes
https://www.readbyqxmd.com/read/27992393/manipulating-the-extracellular-matrix-an-animal-model-of-the-bladder-pain-syndrome
#8
Ifeoma Offiah, Athanasios Didangelos, Barry A OʼReilly, Stephen B McMahon
Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively...
January 2017: Pain
https://www.readbyqxmd.com/read/27979811/high-glucose-facilitated-endothelial-heparanase-transfer-to-the-cardiomyocyte-modifies-its-cell-death-signature
#9
Fulong Wang, Jocelyn Jia, Nathaniel Lal, Dahai Zhang, Amy Pei-Ling Chiu, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
AIMS: The secretion of enzymatically active heparanase (Hep(A)) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (Hep(L)) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of Hep(L) from the endothelial cell (EC), Hep(L) uptake and function can protect the cardiomyocyte by modifying its cell death signature. METHODS AND RESULTS: HG promoted both Hep(L) and Hep(A) secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC...
December 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#10
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27890389/heparanase-confers-a-growth-advantage-to-differentiating-murine-embryonic-stem-cells-and-enhances-oligodendrocyte-formation
#11
Anqi Xiong, Soumi Kundu, Maud Forsberg, Yuyuan Xiong, Tobias Bergström, Tanja Paavilainen, Lena Kjellén, Jin-Ping Li, Karin Forsberg-Nilsson
Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage...
November 23, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27886097/investigating-glycol-split-heparin-derived-inhibitors-of-heparanase-a-study-of-synthetic-trisaccharides
#12
Minghong Ni, Stefano Elli, Annamaria Naggi, Marco Guerrini, Giangiacomo Torri, Maurice Petitou
Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (2) from glucose...
November 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27878294/arctigenin-a-lignan-from-arctium-lappa-l-inhibits-metastasis-of-human-breast-cancer-cells-through-the-downregulation-of-mmp-2-9-and-heparanase-in-mda-mb-231-cells
#13
Chenghua Lou, Zhihui Zhu, Yaping Zhao, Rui Zhu, Huajun Zhao
Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/27853671/heparanase-inhibitors-facilitate-the-assembly-of-the-basement-membrane-in-artificial-skin
#14
Makoto Tsunenaga
Recent research suggests that the basement membrane at the dermal-epidermal junction of the skin plays an important role in maintaining a healthy epidermis and dermis, and repeated damage to the skin can destabilize the skin and accelerate the aging process. Skin-equivalent models are suitable for studying the reconstruction of the basement membrane and its contribution to epidermal homeostasis because they lack the basement membrane and show abnormal expression of epidermal differentiation markers. By using these models, it has been shown that reconstruction of the basement membrane is enhanced not only by supplying basement membrane components, but also by inhibiting proteinases such as urokinase and matrix metalloproteinase...
August 2016: Current Tissue Engineering
https://www.readbyqxmd.com/read/27849593/heparanase-is-required-for-activation-and-function-of-macrophages
#15
Lilach Gutter-Kapon, Dror Alishekevitz, Yuval Shaked, Jin-Ping Li, Ami Aronheim, Neta Ilan, Israel Vlodavsky
The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized and is encouraging the development of heparanase inhibitors as anticancer drugs. Unlike the function of heparanase in cancer cells, very little attention has been given to heparanase contributed by cells composing the tumor microenvironment. Here we used a genetic approach and examined the behavior and function of macrophages isolated from wild-type (WT) and heparanase-knockout (Hpa-KO) mice. Hpa-KO macrophages express lower levels of cytokines (e...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27842848/structural-features-of-heparanase-inhibiting-non-anticoagulant-heparin-derivative-roneparstat
#16
Anna Alekseeva, Giulia Mazzini, Giuseppe Giannini, Annamaria Naggi
Owing to their anti-tumor and anti-inflammatory properties, non-anticoagulant glycol-split (gs) heparins, obtained by periodate oxidation/borohydride reduction, are of growing interest. The present study was focused on the structural characterization of N-acetylated gs-heparin Roneparstat, a promising anti-cancer heparanase-inhibiting drug currently being investigated in clinical trials. The major and minor structural features of structurally complex Roneparstat have been characterized for the first time using conductimetric titration, size-exclusion chromatography with triple detector array, NMR and LC/MS...
January 20, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27828631/expression-of-heparanase-in-basal-cell-carcinoma-and-squamous-cell-carcinoma
#17
Maria Aparecida Silva Pinhal, Maria Carolina Leal Almeida, Alessandra Scorse Costa, Thérèse Rachell Theodoro, Rodrigo Lorenzetti Serrano, Carlos D'Apparecida Santos Machado
Background: Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives: Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control)...
September 2016: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/27804885/the-functions-of-heparanase-in-human-diseases
#18
Hao Jin, Shaobo Zhou
The study of the heparanase has long been paid wide attention. Heparanase ,an endo-β-D-glucuronidase, is capable of specifically degrading heparan sulfate(HS), one of the excellular matrix(ECM) components. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion...
November 1, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27784443/-the-expression-and-significance-of-heparanase-in-oral-squamous-cell-carcinoma-with-different-metastatic-potentials
#19
X B Wu, R Y Wang, Z J Gong, J Yu, S R Zhu
Objective: To detect the expression of heparanase (HPSE) in oral squamous cell carcinoma (OSCC) with different metastatic potentials and investigate its clinical significance. Methods: Transcriptional and translational status of HPSE in OSCC cell lines with different metastatic capacities, primary OSCC samples and their paired metastatic cancer tissues were determined using real-time polymerase chain reaction (PCR) and Western blotting analysis. Immunohistochemistry was used to evaluate HPSE expression in 131 OSCC samples...
October 18, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27783948/macrophage-induced-lymphangiogenesis-and-metastasis-following-paclitaxel-chemotherapy-is-regulated-by-vegfr3
#20
Dror Alishekevitz, Svetlana Gingis-Velitski, Orit Kaidar-Person, Lilach Gutter-Kapon, Sandra D Scherer, Ziv Raviv, Emmanuelle Merquiol, Yael Ben-Nun, Valeria Miller, Chen Rachman-Tzemah, Michael Timaner, Yelena Mumblat, Neta Ilan, David Loven, Dov Hershkovitz, Ronit Satchi-Fainaro, Galia Blum, Jonathan P Sleeman, Israel Vlodavsky, Yuval Shaked
While chemotherapy strongly restricts or reverses tumor growth, the response of host tissue to therapy can counteract its anti-tumor activity by promoting tumor re-growth and/or metastases, thus limiting therapeutic efficacy. Here, we show that vascular endothelial growth factor receptor 3 (VEGFR3)-expressing macrophages infiltrating chemotherapy-treated tumors play a significant role in metastasis. They do so in part by inducing lymphangiogenesis as a result of cathepsin release, leading to VEGF-C upregulation by heparanase...
October 25, 2016: Cell Reports
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