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hyaluronan matrix

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https://www.readbyqxmd.com/read/28081210/mutations-in-hyal2-encoding-hyaluronidase-2-cause-a-syndrome-of-orofacial-clefting-and-cor-triatriatum-sinister-in-humans-and-mice
#1
Martina M A Muggenthaler, Biswajit Chowdhury, S Naimul Hasan, Harold E Cross, Brian Mark, Gaurav V Harlalka, Michael A Patton, Miho Ishida, Elijah R Behr, Sanjay Sharma, Kenneth Zahka, Eissa Faqeih, Brian Blakley, Mike Jackson, Melissa Lees, Vernon Dolinsky, Leroy Cross, Philip Stanier, Claire Salter, Emma L Baple, Fowzan S Alkuraya, Andrew H Crosby, Barbara Triggs-Raine, Barry A Chioza
Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28077237/interplay-of-extracellular-matrix-and-leukocytes-in-lung-inflammation
#2
REVIEW
Thomas N Wight, Charles W Frevert, Jason S Debley, Stephen R Reeves, William C Parks, Steven F Ziegler
During inflammation, leukocytes influx into lung compartments and interact with extracellular matrix (ECM). Two ECM components, versican and hyaluronan, increase in a range of lung diseases. The interaction of leukocytes with these ECM components controls leukocyte retention and accumulation, proliferation, migration, differentiation, and activation as part of the inflammatory phase of lung disease. In addition, bronchial epithelial cells from asthmatic children co-cultured with human lung fibroblasts generate an ECM that is adherent for monocytes/macrophages...
December 23, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/28069922/mechanisms-of-nmda-receptor-and-voltage-gated-l-type-calcium-channel-dependent-hippocampal-ltp-critically-rely-on-proteolysis-that-is-mediated-by-distinct-metalloproteinases
#3
Grzegorz Wiera, Daria Nowak, Inge Van Hove, Piotr Dziegiel, Lieve Moons, Jerzy W Mozrzymas
: Long-term potentiation (LTP) is widely perceived as a memory substrate and in the hippocampal CA3-CA1 pathway, distinct forms of LTP depend on N-methyl-D-aspartate (NMDA) receptors (nmdaLTP) or L-type voltage-gated calcium channels (vdccLTP). Long-term potentiation is also known to be effectively regulated by extracellular proteolysis that is mediated by various enzymes. Herein, we investigated whether in mice hippocampal slices these distinct forms of LTP are specifically regulated by different metalloproteinases (MMPs)...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28053085/inhibition-of-mammalian-glycoprotein-ykl-40-identification-of-the-physiological-ligand
#4
Abhishek A Kognole, Christina M Payne
YKL-40 is a mammalian glycoprotein associated with progression, severity, and prognosis of chronic inflammatory diseases and a multitude of cancers. Despite this well-documented association, identification of the lectin's physiological ligand, and accordingly, biological function, has proven experimentally difficult. YKL-40 has been shown to bind chito-oligosaccharides; however, the production of chitin by the human body has not yet been documented. Possible alternative ligands include proteoglycans, polysaccharides, and fibers like collagen, all of which makeup the extracellular matrix...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28038750/a-tracheal-scaffold-of-gelatin-chondroitin-sulfate-hyaluronan-polyvinyl-alcohol-with-orientated-porous-structure
#5
Xueping Yu, Guowen Qian, Si Chen, Dong Xu, Xiujuan Zhao, Chang Du
Scaffold of gelatin-chondroitin sulfate-hyaluronan-polyvinyl alcohol (GCH-PVA) with orientated microtubule structure and good hydrophilicity was fabricated by unidirectional freeze-drying method mimicking the composition and structure of tracheal cartilage extracellular matrix. PVA was incorporated to improve flexibility and viscoelasticity of GCH scaffold. All wet scaffolds showed similar compressive elastic modulus with native cartilage. GCH-PVA scaffolds showed high relative remaining stress during relaxation indicating good mechanical stability...
March 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28003146/injectable-hyaluronic-acid-down-regulates-interferon-signaling-molecules-igfbp3-and-ifit3-in-the-bovine-intervertebral-disc
#6
Zepur Kazezian, Zhen Li, Mauro Alini, Sibylle Grad, Abhay Pandit
: Low back pain which is a major cause of disability for people aged between 20 and 50 years imposes a serious socio-economic burden. The current focus of regenerative medicine is on identifying molecular markers to facilitate the design of targeted therapeutics. Previously, we have demonstrated that expression of the anti-proliferative interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and pro-apoptotic insulin-like growth factor-binding protein-3 (IGFBP3), are up-regulated as downstream targets of the inflammatory cytokine interferon α (IFNα) signaling pathway in the human annulus fibrosus (AF)...
December 18, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27987780/collagen-glycosaminoglycan-coatings-enhance-new-bone-formation-in-a-critical-size-bone-defect-a-pilot-study-in-rats
#7
Yvonne Förster, Ricardo Bernhardt, Vera Hintze, Stephanie Möller, Matthias Schnabelrauch, Dieter Scharnweber, Stefan Rammelt
Bone regeneration in critical size bone defects still represents an important but unsolved clinical problem. Glycosaminoglycans (GAGs) like chondroitin sulfate (CS) or hyaluronan (HA) are important multifunctional components of the extracellular matrix (ECM) in bone and may stimulate bone healing by recruitment of mesenchymal stromal cells and by supporting their differentiation. Sulfation of GAGs affects their biological activity and thus their interactions with growth factors and/or cells involved in the bone healing process...
February 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/27982477/crosstalk-between-t-lymphocytes-and-lung-fibroblasts-generation-of-a-hyaluronan-enriched-extracellular-matrix-adhesive-for-monocytes
#8
Léa Gaucherand, Ben A Falk, Stephen P Evanko, Gail Workman, Christina K Chan, Thomas N Wight
In immunity and inflammation, T cells are often associated with stromal mesenchymal cells such as fibroblasts. Hyaluronan and proteins that associate with hyaluronan such as versican and tumor necrosis factor-inducible gene-6 (TSG-6) are extracellular matrix (ECM) components that promote leukocyte adhesion, accumulation, and activation. However, the factors responsible for producing this specialized ECM and its impact on inflammatory events are not well understood. In this study, we explored the role of T cells in stimulating lung fibroblasts to produce an ECM that impacts monocyte adhesion...
December 16, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27981209/crohn-s-disease-fibroblasts-overproduce-the-novel-protein-kiaa1199-to-create-proinflammatory-hyaluronan-fragments
#9
Artin Soroosh, Sami Albeiroti, Gail A West, Belinda Willard, Claudio Fiocchi, Carol A de la Motte
BACKGROUND & AIMS: Crohn's Disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Fibrosis, a serious complication of CD, occurs when activated intestinal fibroblasts deposit excessive amounts of extracellular matrix (ECM) in affected areas. A major component of the ECM is high-molecular-weight hyaluronan (HA) that, when depolymerized to low-molecular-weight fragments, becomes proinflammatory and profibrotic. Mechanisms for HA degradation are incompletely understood, but the novel protein KIAA1199 recently was discovered to degrade HA...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27974233/increased-deposition-of-glycosaminoglycans-and-altered-structure-of-heparan-sulfate-in-idiopathic-pulmonary-fibrosis
#10
Gunilla Westergren-Thorsson, Ulf Hedström, Annika Nybom, Emil Tykesson, Emma Åhrman, Marie Hornfelt, Marco Maccarana, Toin H van Kuppevelt, Göran Dellgren, Marie Wildt, Xiao-Hong Zhou, Leif Eriksson, Leif Bjermer, Oskar Hallgren
Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects...
December 11, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27965172/molecular-weight-specific-impact-of-soluble-and-immobilized-hyaluronan-on-cd44-expressing-melanoma-cells-in-3d-collagen-matrices
#11
Jiranuwat Sapudom, Franziska Ullm, Steve Martin, Liv Kalbitzer, Johanna Naab, Stephanie Möller, Matthias Schnabelrauch, Ulf Anderegg, Stephan Schmidt, Tilo Pompe
: Hyaluronan (HA) and its principal receptor CD44 are known to be involved in regulating tumor cell dissemination and metastasis. The direct correlation of CD44-HA interaction on proliferation and invasion of tumor cells in dependence on the molecular weight and the presentation form of HA is not fully understood because of lack of appropriate matrix models. To address this issue, we reconstituted 3D collagen (Coll I) matrices and functionalized them with HA of molecular weight of 30-50kDa (low molecular weight; LMW-HA) and 500-750kDa (high molecular weight; HMW-HA)...
December 10, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27932299/provisional-matrix-a-role-for-versican-and-hyaluronan
#12
REVIEW
Thomas N Wight
Hyaluronan and versican are extracellular matrix (ECM) components that are enriched in the provisional matrices that form during the early stages of development and disease. These two molecules interact to create pericellular "coats" and "open space" that facilitate cell sorting, proliferation, migration, and survival. Such complexes also impact the recruitment of leukocytes during development and in the early stages of disease. Once thought to be inert components of the ECM that help hold cells together, it is now quite clear that they play important roles in controlling cell phenotype, shaping tissue response to injury and maintaining tissue homeostasis...
December 6, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27903619/interleukin-10-mediated-regenerative-postnatal-tissue-repair-is-dependent-on-regulation-of-hyaluronan-metabolism-via-fibroblast-specific-stat3-signaling
#13
Swathi Balaji, Xinyi Wang, Alice King, Louis D Le, Sukanta S Bhattacharya, Chad M Moles, Manish J Butte, Vinicio A de Jesus Perez, Kenneth W Liechty, Thomas N Wight, Timothy M Crombleholme, Paul L Bollyky, Sundeep G Keswani
The cytokine IL-10 has potent antifibrotic effects in models of adult fibrosis, but the mechanisms of action are unclear. Here, we report a novel finding that IL-10 triggers a signal transducer and activator of transcription 3 (STAT3)-dependent signaling pathway that regulates hyaluronan (HA) metabolism and drives adult fibroblasts to synthesize an HA-rich pericellular matrix, which mimics the fetal regenerative wound healing phenotype with reduced fibrosis. By using cre-lox-mediated novel, inducible, fibroblast-, keratinocyte-, and wound-specific STAT3 knockdown postnatal mice-plus syngeneic fibroblast cell-transplant models-we demonstrate that the regenerative effects of IL-10 in postnatal wounds are dependent on HA synthesis and fibroblast-specific STAT3-dependent signaling...
November 30, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27895126/versican-deficiency-significantly-reduces-lung-inflammatory-response-induced-by-polyinosine-polycytidylic-acid-stimulation
#14
Inkyung Kang, Ingrid A Harten, Mary Y Chang, Kathleen R Braun, Alyssa Sheih, Mary P Nivison, Pamela Y Johnson, Gail Workman, Gernot Kaber, Stephen P Evanko, Christina K Chan, Mervyn J Merrilees, Steven F Ziegler, Michael G Kinsella, Charles W Frevert, Thomas N Wight
Viral infection is an exacerbating factor contributing to chronic airway diseases, such as asthma, via mechanisms that are still unclear. Polyinosine-polycytidylic acid (poly(I:C)), a Toll-like receptor 3 (TLR3) agonist used as a mimetic to study viral infection, has been shown to elicit inflammatory responses in lungs and to exacerbate pulmonary allergic reactions in animal models. Previously, we have shown that poly(I:C) stimulates lung fibroblasts to accumulate an extracellular matrix (ECM), enriched in hyaluronan (HA) and its binding partner versican, which promotes monocyte adhesion...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27886639/hyaluronan-derived-swelling-of-solid-tumors-the-contribution-of-collagen-and-cancer-cells-and-implications-for-cancer-therapy
#15
Chrysovalantis Voutouri, Christiana Polydorou, Panagiotis Papageorgis, Vasiliki Gkretsi, Triantafyllos Stylianopoulos
Despite the important role that mechanical forces play in tumor growth and therapy, the contribution of swelling to tumor mechanopathology remains unexplored. Tumors rich in hyaluronan exhibit a highly negative fixed charge density. Repulsive forces among these negative charges as well as swelling of cancer cells due to regulation of intracellular tonicity can cause tumor swelling and development of stress that might compress blood vessels, compromising tumor perfusion and drug delivery. Here, we designed an experimental strategy, using four orthotopic tumor models, to measure swelling stress and related swelling to extracellular matrix components, hyaluronan and collagen, as well as to tumor perfusion...
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27884164/hyaluronan-synthase-2-expressed-by-cancer-associated-fibroblasts-promotes-oral-cancer-invasion
#16
Ziwen Zhang, Detao Tao, Ping Zhang, Xue Liu, Yuchao Zhang, Jie Cheng, Hua Yuan, Laikui Liu, Hongbing Jiang
BACKGROUND: Hyaluronan synthases (HAS) control the biosynthesis of hyaluronan (HA) and critically modulate the tumor microenviroment. Cancer-associated fibroblasts (CAFs) affect the progression of a tumor by remolding the matrix. However, little is known about the role of HAS from CAFs in this process. This study aimed to determine the role of hyaluronan synthase 2 (HAS2) from CAFs in the progression of oral squamous cell carcinoma (OSCC) invasion. METHODS: HAS isoforms 1, 2, and 3 in paired sets of CAFs and normal fibroblasts (NFs) were examined by real-time PCR, and the expression of HAS2 and α-SMA in OSCC tissue sections was further evaluated using immunohistochemical staining...
November 25, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27875656/involvement-of-jnk-in-tnf%C3%AE-driven-remodelling
#17
Irene Mj Eurlings, Niki L Reynaert, Cheryl van de Wetering, Scott W Aesif, Evi M Mercken, Rafael de Cabo, Jos L van der Velden, Yvonne M Janssen-Heininger, Emiel F M Wouters, Mieke A Dentener
Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is characterized by airway wall thickening and/or emphysema. Although the bronchial and alveolar compartments are functionally independent entities, we recently showed comparable alterations in matrix composition comprised of decreased elastin content and increased collagen and hyaluronan contents of alveolar and small airway walls. Out of several animal models tested SPC-TNFα mice showed remodelling in alveolar and airway walls similar to what is observed in COPD patients...
November 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27869206/endotoxin-free-hyaluronan-and-hyaluronan-fragments-do-not-stimulate-tnf-%C3%AE-interleukin-12-or-upregulate-co-stimulatory-molecules-in-dendritic-cells-or-macrophages
#18
Yifei Dong, Arif Arif, Mia Olsson, Valbona Cali, Blair Hardman, Manisha Dosanjh, Mark Lauer, Ronald J Midura, Vincent C Hascall, Kelly L Brown, Pauline Johnson
The extracellular matrix glycosaminoglycan, hyaluronan, has been described as a regulator of tissue inflammation, with hyaluronan fragments reported to stimulate innate immune cells. High molecular mass hyaluronan is normally present in tissues, but upon inflammation lower molecular mass fragments are generated. It is unclear if these hyaluronan fragments induce an inflammatory response or are a consequence of inflammation. In this study, mouse bone marrow derived macrophages and dendritic cells (DCs) were stimulated with various sizes of hyaluronan from different sources, fragmented hyaluronan, hyaluronidases and heavy chain modified-hyaluronan (HA-HC)...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27867002/trametinib-plus-4-methylumbelliferone-exhibits-antitumor-effects-by-erk-blockade-and-cd44-downregulation-and-affects-pd1-and-pd-l1-in-malignant-pleural-mesothelioma
#19
Hiroyuki Cho, Seiji Matsumoto, Yoshiko Fujita, Ayumi Kuroda, Toshi Menju, Makoto Sonobe, Nobuyuki Kondo, Ikuko Torii, Takashi Nakano, Primo N Lara, David R Gandara, Hiroshi Date, Seiki Hasegawa
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy in which the mitogen-activated protein kinase (MAPK) pathway plays a critical role in the regulation of tumorigenesis. Hyaluronan (HA) is a major component of the extracellular matrix, and elevated HA levels, with a concurrent increase in malignant properties, are associated with MPM. METHODS: We evaluated the effects of trametinib, a MAPK kinase enzyme (MEK) inhibitor, and 4-methylumbelliferone (4-MU), an HA synthesis inhibitor, alone and in combination on MPM cells in vitro and in vivo...
November 17, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27846148/4-methylumbelliferone-suppresses-hyaluronan-synthesis-and-tumor-progression-in-scid-mice-intra-abdominally-inoculated-with-pancreatic-cancer-cells
#20
Hayato Nagase, Daisuke Kudo, Akiko Suto, Eri Yoshida, Shinichiro Suto, Mika Negishi, Ikuko Kakizaki, Kenichi Hakamada
OBJECTIVES: Pancreatic ductal adenocarcinoma contains large amounts of the glycosaminoglycan hyaluronan (HA), which is involved in various physiological processes. Here, we aimed to clarify the anticancer mechanisms of 4-methylumbelliferone (MU), a well-known HA synthesis inhibitor. METHODS: MIA PaCa-2 human pancreatic cancer cells were used. We evaluated cellular proliferation, migration, and invasion in the presence of MU, exogenous HA, and an anti-CD44 antibody...
February 2017: Pancreas
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