42 results match your criteria morphogens inflammation


The foggy world(s) of p63 isoform regulation in normal cells and cancer.

J Pathol 2021 Feb 26. Epub 2021 Feb 26.

Research Centre of Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Brno, Czech Republic.

The p53 family member p63 exists as two major protein variants (TAp63 and ΔNp63) with distinct expression patterns and functional properties. Whilst downstream target genes of p63 have been studied intensively, how p63 variants are themselves controlled has been relatively neglected. Here, we review advances in understanding ΔNp63 and TAp63 regulation, highlighting their distinct pathways. Read More

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February 2021

Cell-surface heparan sulfate proteoglycans as multifunctional integrators of signaling in cancer.

Cell Signal 2021 Jan 3;77:109822. Epub 2020 Nov 3.

Department of Gynecology and Obstetrics, Münster University Hospital, Münster, Germany. Electronic address:

Proteoglycans (PGs) represent a large proportion of the components that constitute the extracellular matrix (ECM). They are a diverse group of glycoproteins characterized by a covalent link to a specific glycosaminoglycan type. As part of the ECM, heparan sulfate (HS)PGs participate in both physiological and pathological processes including cell recruitment during inflammation and the promotion of cell proliferation, adhesion and motility during development, angiogenesis, wound repair and tumor progression. Read More

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January 2021

GLIS3 Transcriptionally Activates WNT Genes to Promote Differentiation of Human Embryonic Stem Cells into Posterior Neural Progenitors.

Stem Cells 2019 02 2;37(2):202-215. Epub 2018 Dec 2.

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.

Anterior-posterior (A-P) specification of the neural tube involves initial acquisition of anterior fate followed by the induction of posterior characteristics in the primitive anterior neuroectoderm. Several morphogens have been implicated in the regulation of A-P neural patterning; however, our understanding of the upstream regulators of these morphogens remains incomplete. Here, we show that the Krüppel-like zinc finger transcription factor GLI-Similar 3 (GLIS3) can direct differentiation of human embryonic stem cells (hESCs) into posterior neural progenitor cells in lieu of the default anterior pathway. Read More

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February 2019

Zika Virus Can Strongly Infect and Disrupt Secondary Organizers in the Ventricular Zone of the Embryonic Chicken Brain.

Cell Rep 2018 Apr;23(3):692-700

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address:

Zika virus (ZIKV) is associated with severe neurodevelopmental impairments in human fetuses, including microencephaly. Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in nonuniform periventricular infection 3 days later. Read More

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The multifaceted roles of perlecan in fibrosis.

Matrix Biol 2018 08 20;68-69:150-166. Epub 2018 Feb 20.

Graduate School of Biomedical Engineering, UNSW Sydney, NSW 2052, Australia.

Perlecan, or heparan sulfate proteoglycan 2 (HSPG2), is a ubiquitous heparan sulfate proteoglycan that has major roles in tissue and organ development and wound healing by orchestrating the binding and signaling of mitogens and morphogens to cells in a temporal and dynamic fashion. In this review, its roles in fibrosis are reviewed by drawing upon evidence from tissue and organ systems that undergo fibrosis as a result of an uncontrolled response to either inflammation or traumatic cellular injury leading to an over production of a collagen-rich extracellular matrix. This review focuses on examples of fibrosis that occurs in lung, liver, kidney, skin, kidney, neural tissues and blood vessels and its link to the expression of perlecan in that particular organ system. Read More

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Thyroid hormone in the regulation of hepatocellular carcinoma and its microenvironment.

Cancer Lett 2018 04;419:175-186

Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston (SC), USA; Section of Gastroenterology, Ralph H Johnson Veteran Affairs Medical Center, Charleston (SC), USA. Electronic address:

Hepatocellular carcinoma (HCC) commonly arises from a liver damaged by extensive inflammation and fibrosis. Various factors including cytokines, morphogens, and growth factors are involved in the crosstalk between HCC cells and the stromal microenvironment. Increasing our understanding of how stromal components interact with HCC and the signaling pathways involved could help identify new therapeutic and/or chemopreventive targets. Read More

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Delivery of cellular factors to regulate bone healing.

Adv Drug Deliv Rev 2018 04 31;129:285-294. Epub 2018 Jan 31.

Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Switzerland. Electronic address:

Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate and complex interplay of cellular and molecular processes, which tightly involve the immune system. Pathological settings of anatomical, biomechanical or inflammatory nature may lead to impaired bone healing. Innovative strategies to enhance bone repair, including the delivery of osteoprogenitor cells or of potent cytokines/morphogens, indicate the potential of 'orthobiologics', but are not fully satisfactory. Read More

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Syndecans in chronic inflammatory and autoimmune diseases: Pathological insights and therapeutic opportunities.

J Cell Physiol 2018 09 25;233(9):6346-6358. Epub 2018 Mar 25.

Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington.

Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues. There are four mammalian syndecans, SDC-1 thorough 4, which play a critical role in cell adhesion, migration, proliferation, differentiation, and angiogenesis through independent and growth factor mediated signaling. An altered expression of SDCs is often observed in autoimmune disorders, cancer, HIV infection, and many other pathological conditions. Read More

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September 2018

Genetic deficiency of Wnt5a diminishes disease severity in a murine model of rheumatoid arthritis.

Arthritis Res Ther 2017 07 19;19(1):166. Epub 2017 Jul 19.

Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany Street, W-611, Boston, MA, 02118, USA.

Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Despite the recent successes of disease-modifying anti-rheumatic drugs (DMARDs), there is still clinical need for understanding the development and molecular etiology of RA. Wnts are developmental morphogens whose roles in adult pathology are poorly characterized. Read More

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Wnt signaling in cardiovascular disease: opportunities and challenges.

Curr Opin Lipidol 2017 Oct;28(5):387-396

Department of Internal Medicine-Endocrine Division, UT Southwestern Medical Center, Dallas, Texas, USA.

Purpose Of Review: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis.

Recent Findings: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease. Read More

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October 2017

Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness.

World J Hepatol 2017 Mar;9(9):455-468

Simone Brivio, Massimiliano Cadamuro, Mario Strazzabosco, School of Medicine and Surgery, University of Milan-Bicocca, 20900 Monza, Italy.

Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases). Read More

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Tumour-necrosis factor-α induces heparan sulfate 6-O-endosulfatase 1 (Sulf-1) expression in fibroblasts.

Int J Biochem Cell Biol 2016 11 28;80:57-65. Epub 2016 Sep 28.

University of Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France. Electronic address:

Heparan sulfate (HS) 6-O-endosulfatases (Sulfs) have emerged recently as critical regulators of many physiological and pathological processes. By removing 6-O-sulfates from specific HS sequences, they modulate the activities of a variety of growth factors and morphogens, including fibroblast growth factor (FGF)-1. However, little is known about the functions of Sulfs in inflammation. Read More

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November 2016

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology.

Neuropharmacology 2016 Nov 24;110(Pt B):605-625. Epub 2015 Jun 24.

Biology Department, Trinity Washington University, Washington, DC, USA.

White matter disease afflicts both developing and mature central nervous systems. Both cell intrinsic and extrinsic dysregulation result in profound changes in cell survival, axonal metabolism and functional performance. Experimental models of developmental white matter (WM) injury and demyelination have not only delineated mechanisms of signaling and inflammation, but have also paved the way for the discovery of pharmacological approaches to intervention. Read More

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November 2016

Multitasking Human Lectin Galectin-3 Interacts with Sulfated Glycosaminoglycans and Chondroitin Sulfate Proteoglycans.

Biochemistry 2016 08 2;55(32):4541-51. Epub 2016 Aug 2.

Laboratory of Mechanistic Glycobiology, Department of Chemistry, ‡Department of Biological Sciences, §Life Science and Technology Institute, Michigan Technological University , Houghton, Michigan 49931, United States.

Glycosaminoglycan (GAG) binding proteins (GAGBPs), including growth factors, cytokines, morphogens, and extracellular matrix proteins, interact with both free GAGs and those covalently linked to proteoglycans. Such interactions modulate a variety of cellular and extracellular events, such as cell growth, metastasis, morphogenesis, neural development, and inflammation. GAGBPs are structurally and evolutionarily unrelated proteins that typically recognize internal sequences of sulfated GAGs. Read More

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Minireview: Syndecans and their crucial roles during tissue regeneration.

FEBS Lett 2016 08 15;590(15):2408-17. Epub 2016 Jul 15.

Department of Biomedical Sciences and Biotech Research & Innovation Center, University of Copenhagen, Denmark.

Syndecans are transmembrane heparan sulfate proteoglycans, with roles in development, tumorigenesis and inflammation, and growing evidence for involvement in tissue regeneration. This is a fast developing field with the prospect of utilizing tissue engineering and biomaterials in novel therapies. Syndecan receptors are not only ubiquitous in mammalian tissues, regulating cell adhesion, migration, proliferation, and differentiation through independent signaling but also working alongside other receptors. Read More

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Dentin Dysplasia in Notum Knockout Mice.

Vet Pathol 2016 07 29;53(4):853-62. Epub 2016 Feb 29.

Metabolism, Lexicon Pharmaceuticals Inc, The Woodlands, TX, USA.

Secreted WNT proteins control cell differentiation and proliferation in many tissues, and NOTUM is a secreted enzyme that modulates WNT morphogens by removing a palmitoleoylate moiety that is essential for their activity. To better understand the role this enzyme in development, the authors produced NOTUM-deficient mice by targeted insertional disruption of the Notum gene. The authors discovered a critical role for NOTUM in dentin morphogenesis suggesting that increased WNT activity can disrupt odontoblast differentiation and orientation in both incisor and molar teeth. Read More

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Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?

J Clin Med 2015 Dec 19;4(12):2028-41. Epub 2015 Dec 19.

School of Medicine and Surgery, University of Milan-Bicocca, Via Cadore 48, 20900 Monza, Italy.

In addition to its well-established role in embryo development, epithelial-to-mesenchymal transition (EMT) has been proposed as a general mechanism favoring tumor metastatization in several epithelial malignancies. Herein, we review the topic of EMT in cholangiocarcinoma (CCA), a primary liver cancer arising from the epithelial cells lining the bile ducts (cholangiocytes) and characterized by an abundant stromal reaction. CCA carries a dismal prognosis, owing to a pronounced invasiveness and scarce therapeutic opportunities. Read More

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December 2015

Time- and compartment-resolved proteome profiling of the extracellular niche in lung injury and repair.

Mol Syst Biol 2015 Jul 14;11(7):819. Epub 2015 Jul 14.

Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany

The extracellular matrix (ECM) is a key regulator of tissue morphogenesis and repair. However, its composition and architecture are not well characterized. Here, we monitor remodeling of the extracellular niche in tissue repair in the bleomycin-induced lung injury mouse model. Read More

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Metabolic reprogramming and cell fate regulation in alcoholic liver disease.

Pancreatology 2015 Jul 10;15(4 Suppl):S61-5. Epub 2015 Mar 10.

Southern California Research Center ALPD and Cirrhosis and Department of Pathology, Keck School of Medicine of the University of Southern California, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA. Electronic address:

Unlabelled: Alcoholic liver disease (ALD) should be defined as a life-style metabolic disease. Its pathogenesis is driven by altered cell fate of both parenchymal and non-parenchymal liver cell types, contributing to different pathologic spectra. A critical turning point in progression of ALD is chronic alcoholic steatohepatitis (ASH) or alcoholic neutrophilic hepatitis (AH), which markedly predisposes patients to most devastating ALD sequela, cirrhosis and liver cancer. Read More

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Of plasticity and specificity: dialectics of the microenvironment and macroenvironment and the organ phenotype.

Wiley Interdiscip Rev Dev Biol 2014 Mar-Apr;3(2):147-63. Epub 2013 Nov 18.

Department of Cancer & DNA Damage Responses, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

The study of biological form and how it arises is the domain of the developmental biologists; but once the form is achieved, the organ poses a fascinating conundrum for all the life scientists: how are form and function maintained in adult organs throughout most of the life of the organism? That they do appears to contradict the inherently plastic nature of organogenesis during development. How do cells with the same genetic information arrive at, and maintain such different architectures and functions, and how do they keep remembering that they are different from each other? It is now clear that narratives based solely on genes and an irreversible regulatory dynamics cannot answer these questions satisfactorily, and the concept of microenvironmental signaling needs to be added to the equation. During development, cells rearrange and differentiate in response to diffusive morphogens, juxtacrine signals, and the extracellular matrix (ECM). Read More

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January 2015

Of plasticity and specificity: dialectics of the micro- and macro-environment and the organ phenotype.

Wiley Interdiscip Rev Membr Transp Signal 2014 ;3(2):147-163

Department of Cancer & DNA Damage Responses; Life Sciences Division; Lawrence Berkeley National Laboratory; Berkeley, CA, 94720, USA.

The study of biological form and how it arises is the domain of the developmental biologists; but once the form is achieved, the organ poses a fascinating conundrum for all the life scientists: how are form and function maintained in adult organs throughout most of the life of the organism? That they do appears to contradict the inherently plastic nature of organogenesis during development. How do cells with the same genetic information arrive at, and maintain such different architectures and functions, and how do they keep remembering that they are different from each other? It is now clear that narratives based solely on genes and an irreversible regulatory dynamics cannot answer these questions satisfactorily, and the concept of microenvironmental signaling needs to be added to the equation. During development, cells rearrange and differentiate in response to diffusive morphogens, juxtacrine signals and the extracellular matrix (ECM). Read More

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January 2014

Interaction of chondroitin sulfate and dermatan sulfate from various biological sources with heparin-binding growth factors and cytokines.

Glycoconj J 2013 Aug 29;30(6):619-32. Epub 2012 Dec 29.

Laboratory of Proteoglycan Signaling and Therapeutics, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University Graduate School of Life Science, West-11, North-21, Kita-ku, Sapporo, Hokkaido, 001-0021, Japan.

Chondroitin sulfate (CS) and dermatan sulfate (DS) interact with various extracellular molecules such as growth factors, cytokines/chemokines, neurotrophic factors, morphogens, and viral proteins, thereby playing roles in a variety of biological processes including cell adhesion, proliferation, tissue morphogenesis, neurite outgrowth, infections, and inflammation/leukocyte trafficking. CS/DS are modified with sulfate groups at C-2 of uronic acid residues as well as C-4 and/or C-6 of N-acetyl-D-galactosamine residues, yielding enormous structural diversity, which enables the binding with numerous proteins. We have demonstrated that highly sulfated CS-E from squid cartilage, for example, interacts with heparin-binding proteins including midkine, pleiotrophin, and fibroblast growth factors expressed in brain with high affinity (Kd values in the nM range). Read More

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Syndecans in cartilage breakdown and synovial inflammation.

Nat Rev Rheumatol 2013 Jan 23;9(1):43-55. Epub 2012 Oct 23.

Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Domagkstraße 3, D-48149 Münster, Germany.

Syndecans are transmembrane heparan sulphate proteoglycans (HSPGs) that have gained increasing interest as regulators of a variety of tissue responses, including cartilage development and remodelling. These proteoglycans are composed of a core protein to which extracellular glycosaminoglycan (GAG) chains are attached. Through these GAG chains, syndecans can interact with a variety of extracellular matrix molecules and bind to a number of soluble mediators including morphogens, growth factors, chemokines and cytokines. Read More

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January 2013

Wnt/beta-catenin signaling and small molecule inhibitors.

Curr Pharm Des 2013 ;19(4):634-64

SFI-CAST Biomedical Innovation Center, Unit for Cell Signaling, Oslo University Hospital,Forskningsparken, Gaustadalleén 21, 0349, Oslo, Norway.

Wnt/β-catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, β-catenin, serves several cellular functions. Read More

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The crucial role of cholangiocytes in cholangiopathies.

Authors:
Seon Mee Park

Gut Liver 2012 Jul 2;6(3):295-304. Epub 2012 May 2.

Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Korea.

Cholangiopathies are diseases involving the intrahepatic biliary tree. They appear to involve, chronic inflammation of the bile ducts, which can lead to the development of bile duct cholestasis, proliferation/ductopenia, biliary fibrosis, and malignant transformation. Sustained stimulatory insults to biliary epithelial cells can induce a ductular reaction, which has a key role in the initiation and progression of cholangiopathies. Read More

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Microvesicles: potential markers and mediators of endothelial dysfunction.

Curr Opin Endocrinol Diabetes Obes 2012 Apr;19(2):121-7

Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.

Purpose Of Review: Microvesicles (also known as microparticles) are small membranous structures that are released from platelets and cells upon activation or during apoptosis. Microvesicles have been found in blood, urine, synovial fluid, extracellular spaces of solid organs, atherosclerotic plaques, tumors, and elsewhere. Here, we focus on new clinical and basic work that implicates microvesicles as markers and mediators of endothelial dysfunction and hence novel contributors to cardiovascular and other diseases. Read More

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Hedgehog signaling in cholangiocytes.

Curr Opin Gastroenterol 2011 May;27(3):268-75

Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Purpose Of Review: Cells lining the biliary tree are targets of injury, but also orchestrate liver repair. The latter involves autocrine/paracrine signaling that enhances the viability and growth of residual ductular cells and promotes accumulation of inflammatory and myofibroblastic cells. The mechanisms mediating this so-called 'ductular reaction' need to be better understood to improve injury outcomes. Read More

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Inhibition of bone morphogenetic proteins protects against atherosclerosis and vascular calcification.

Circ Res 2010 Aug 24;107(4):485-94. Epub 2010 Jun 24.

Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1679, USA.

Rationale: The bone morphogenetic proteins (BMPs), a family of morphogens, have been implicated as mediators of calcification and inflammation in the vascular wall.

Objective: To investigate the effect of altered expression of matrix Gla protein (MGP), an inhibitor of BMP, on vascular disease.

Methods And Results: We used MGP transgenic or MGP-deficient mice bred to apolipoprotein E mice, a model of atherosclerosis. Read More

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Stimulated neovascularization, inflammation resolution and collagen maturation in healing rat cutaneous wounds by a heparan sulfate glycosaminoglycan mimetic, OTR4120.

Wound Repair Regen 2009 Nov-Dec;17(6):840-52

Department of Plastic and Reconstructive Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Heparan sulfate glycosaminoglycans (HS-GAGs) are not only the structural elements of tissue architecture but also regulate the bioavailability and transduction pathways of heparan sulfate-bound polypeptides released by cells or the extracellular matrix. Heparan sulfate-bound polypeptides include inflammatory mediators, chemokines, angiogenic factors, morphogens, and growth-promoting factors that induce cell migration, proliferation, and differentiation in wound healing. OTR4120, a polymer engineered to mimic the properties of HS-GAGs, is used to replace the natural HS-GAGs that are degraded during wound repair, and enhance the tissue regeneration by preserving the cellular microenvironment and the endogenous signals needed for tissue regeneration. Read More

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Cancer morphogenesis: role of mitochondrial failure.

Authors:
Egil Fosslien

Ann Clin Lab Sci 2008 ;38(4):307-29

Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

Adenosine triphosphate (ATP) required for normal cell metabolism is mainly supplied by mitochondrial oxidative phosphorylation (OXPHOS), which is limited by available oxygen and modulated by cell signaling pathways. Primary or secondary OXPHOS failure shifts cell metabolism towards ATP generation by glycolysis (Warburg effect). The objective of this paper is to clarify the role of mitochondrial dysfunction in cancer morphogenesis and to elucidate how faulty morphogen gradient signaling and inflammatory mediators that regulate OXPHOS can cause cancer-induced morphogenesis. Read More

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January 2009