Abstracts tagged "Fibroblasts"

Abstract Number: 1659 • 2012 ACR/ARHP Annual Meeting
Ptpome Profile of Rheumatoid Arthritis Fibroblast-Like Synoviocytes: A Novel Role for the Tyrosine Phosphatase SHP-2 As a Modulator of Invasion and Survival
Stephanie Stanford¹, Michael Maestre², Beatrix Bartok³, David L. Boyle⁴, Heather Arnett⁵, Tomas Mustelin⁶, Gary S. Firestein⁷ and Nunzio Bottini², ¹Cellular Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, ²La Jolla Institute for Allergy and Immunology, La Jolla, CA, ³Rheumatology, UCSD School of Medicine, La Jolla, CA, ⁴Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, La Jolla, CA, ⁵Amgen, Inc., Seattle, WA, ⁶Sanford-Burnham Institute for Medical Research, La Jolla, CA, ⁷Div of Rheumatology, UCSD School of Medicine, La Jolla, CA
Background/Purpose: Fibroblast-like synoviocytes (FLS) in the synovial intimal lining are key mediators of inflammation and joint destruction in rheumatoid arthritis (RA). These cells assume a…
Abstract Number: 1610 • 2012 ACR/ARHP Annual Meeting
The DNA Methylation Signature in Fibroblast-Like Synoviocytes (FLS) Defines Critical Pathogenic Pathways in Rheumatoid Arthritis (RA)
David L. Boyle¹, Robert Shoemaker², David W. Anderson³, Wei Wang⁴ and Gary S. Firestein⁵, ¹Div of Rheum, UCSD School of Medicine, La Jolla, CA, ²NexDx, Inc., San Diego, CA, ³Research and Development, NexDx, Inc., San Diego, CA, ⁴Chemistry, UCSD, La Jolla, CA, ⁵Div of Rheumatology, UCSD School of Medicine, La Jolla, CA
Background/Purpose: A DNA methylation signature has been characterized that distinguishes RA FLS from osteoarthritis (OA) and normal (NL) FLS. The presence of epigenetic changes in…
Abstract Number: 1517 • 2012 ACR/ARHP Annual Meeting
TLR9 Signaling in Fibroblasts Promotes Pro-Fibrotic Responses Via TGF-Beta
Yang Yang¹, Feng Fang², Lei Liu¹, Junjie Shangguan³, Boping Ye¹ and John Varga³, ¹School of Life Science and Technology, China Pharmaceutical University, Nanjing, China, ²Rheumatology Division, Northwestern University, Chicago, IL, ³Division of Rheumatology, Northwestern University, Chicago, IL
Background/Purpose: Systemic sclerosis (SSc) is associated with progressive fibrosis and transforming growth factor β (TGF-β) is implicated in its pathogenesis. Toll-like receptors (TLR) respond to…
Abstract Number: 1499 • 2012 ACR/ARHP Annual Meeting
The Soluble Guanylate Cyclase Mediates Its Anti-Fibrotic Effects by Inhibiting TGF-β Signaling
Christian Beyer¹, Sonia C. Schindler², Alfiya Distler³, Clara Dees⁴, Helena Reichert², Hümeyra Akan², Peter Sandner⁵, Oliver Distler⁶, Georg Schett⁷ and Joerg HW Distler³, ¹Department of Internal Medicine 3, Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ²Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany, ³Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ⁴Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ⁵Bayer Health Care, Global Drug Discovery – Common Mechanism Research, Bayer Health Care, Global Drug Discovery – Common Mechanism Research, Wuppertal, Germany, ⁶Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland, ⁷Dept of Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
Background/Purpose: We have recently demonstrated that stimulation of the soluble guanylate cyclase (sGC) has potent anti-fibrotic activity in different models of fibrosis. sGC stimulation increases…
Abstract Number: 1500 • 2012 ACR/ARHP Annual Meeting
Activation of Pregnane X Receptor Induces Regression of Experimental Dermal Fibrosis
Christian Beyer¹, Alla Skapenko², Alfiya Distler³, Clara Dees⁴, Helena Reichert⁵, Louis E. Munoz³, Jan Leipe⁶, Hendrik Schulze-Koops⁷, Oliver Distler⁸, Georg Schett⁹ and Joerg HW Distler³, ¹Department of Internal Medicine 3, Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ²Division of Rheumatology and Clinical Immunology, Med. Poliklinik,, University of Munich, Munich, Germany, ³Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ⁴Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ⁵Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany, ⁶Med. Poliklinik, University of Munich, Division of Rheumatology and Clinical Immunology, Munich, Germany, ⁷University of Munich, Munich, Germany, ⁸Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland, ⁹Dept of Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
Background/Purpose: Pregnane-X-receptor (PXR) belongs to a superfamily of nuclear receptors that function as ligand-activated transcriptional factors. Although endogenous ligands have not yet been identified, PXR…
Abstract Number: 1505 • 2012 ACR/ARHP Annual Meeting
Inactivation of Tankyrases Ameliorates Canonical Wnt Signaling and Prevents Experimental Fibrosis
Alfiya Distler¹, Lisa Deloch², Jingang Huang², Clara Dees², Neng Yu Lin², Christian Beyer³, Oliver Distler⁴, Georg A. Schett⁵ and Joerg HW Distler¹, ¹Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ²Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ³Department of Internal Medicine 3, Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ⁴Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland, ⁵Dept of Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
Background/Purpose: Systemic sclerosis (SSc) is characterized by aberrant activation of fibroblasts with increased release of extracellular matrix components. Canonical Wnt signaling has recently emerged as…
Abstract Number: 1492 • 2012 ACR/ARHP Annual Meeting
IL-13 Receptors and Signaling in the Dermal Fibroblasts From Patients with Systemic Sclerosis
Yuko Ota¹, Yasushi Kawaguchi¹, Atsushi Kitani², Kae Takagi¹, Hisae Ichida¹, Yasuhiro Katsumata¹, Takahisa Gono¹, Masanori Hanaoka¹, Yuko Okamoto¹ and Hisashi Yamanaka¹, ¹Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, ²Mucosal Immunity Section, NIAID/NIH, Bethesda, MD
Background/Purpose: Interleukin (IL)-13 is a pleiotropic cytokine involved in T helper type 2 cell immune response and in the development of fibrotic conditions such as…
Abstract Number: 2309 • 2012 ACR/ARHP Annual Meeting
Increased Levels of Ser 181 Phosphorylated SOX9 in SSc Dermal Fibroblasts: A Novel Participant in the Pathogenesis of SSc Fibrotic Process
Sonsoles Piera-Velazquez, Jolanta Fertala and Sergio A. Jimenez, Jefferson Institute of Molecular Medicine, Division of Connective Tissue Diseases and Scleroderma Center,Thomas Jefferson University, Philadelphia, PA
Background/Purpose: SOX9, a high mobility group (HMG) transcription factor is a master regulator of chondrogenesis and is essential for the maintenance of the chondrocyte-specific phenotype…
Abstract Number: 1496 • 2012 ACR/ARHP Annual Meeting
Downregulated Expression of Metallothionein Genes in Response to the Gadolinium Contrast Agent Omniscan in Normal Human Differentiated Macrophages and Dermal Fibroblasts
Peter J. Wermuth¹, Francesco Del Galdo², Sankar Addya³, Paolo Fortina³ and Sergio A. Jimenez¹, ¹Jefferson Institute of Molecular Medicine, Division of Connective Tissue Diseases and Scleroderma Center,Thomas Jefferson University, Philadelphia, PA, ²Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, ³Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA
Background/Purpose: Metallothioneins bind heavy metals with high affinity and can serve as storage proteins for labile Zn2+ which in turn can regulate immune system activity…
Abstract Number: 2289 • 2012 ACR/ARHP Annual Meeting
Adiponectin Has Potent Anti-Fibrotic Effects Mediated Via AMP Kinase: Novel Target for Fibrosis Therap
Feng Fang¹, Lei Liu², Yang Yang², Jun Wei¹, Swati Bhattacharyya³, Ross Summer⁴, Boping Ye² and John Varga³, ¹Rheumatology Division, Northwestern University, Chicago, IL, ²School of Life Science and Technology, China Pharmaceutical University, Nanjing, China, ³Division of Rheumatology, Northwestern University, Chicago, IL, ⁴Pulmonary Center, Boston University, Boston, MA
Background/Purpose: Fibrosis in scleroderma is associated with transforming growth factor-β (TGF-β) signaling activation, collagen deposition and myofibroblast accumulation. Peroxisome proliferator activated receptor gamma (PPAR-γ) inhibits…
Abstract Number: 1193 • 2012 ACR/ARHP Annual Meeting
Podoplanin Expression in Rheumatoid Stroma Correlates with Lymphoid Neogenesis and Is Downregulated by Anti-TNF-α Therapy
Regina Faré¹, Elena Izquierdo¹, Manuel J. Del Rey¹, Raquel Celis², Alicia Usategui¹, Juan D. Cañete³ and Jose L. Pablos¹, ¹Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (I+12), Madrid, Spain, ²Arthritis Unit, Rheumatology Department, Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona and IDIBAPS, Barcelona, Spain, ³Rheumatology, Hospital Clínic of Barcelona. IDIBAPS. University of Barcelona, Barcelona, Spain
Background/Purpose: In rheumatoid arthritis (RA), synovial fibroblasts (SF) expand and undergo phenotypic changes that contribute to chronic inflammation and joint destruction. Podoplanin (Pdp) is a…
Abstract Number: 2293 • 2012 ACR/ARHP Annual Meeting
Interleukin-17A Positive Cells Are Increased in Systemic Sclerosis Skin and Their Number Is Inversely Correlated to Skin Thickness
Marie-Elise Truchetet¹, Nicolò Costantino Brembilla¹, Elisa Montanari¹, Paola Lonati², Pier Luigi Meroni³ and Carlo Chizzolini¹, ¹University hospital of Geneva, Geneva, Switzerland, ²Division of Rheumatology, Istituto G. Pini, University of Milan, Milan, Italy, ³Division of Rheumatology, Istituto G. Pini, University of Milan, Milano, Italy
Background/Purpose: T cell producing IL-17A are increased in the peripheral blood of individuals affected by systemic sclerosis (SSc). We asked the question whether IL-17A-producing cells…
Abstract Number: 891 • 2012 ACR/ARHP Annual Meeting
Fatty Acids Promote Secretion of Proinflammatory and Prodestructive Factors by Synovial Fibroblasts
Klaus W. Frommer¹, Andreas Schäffler², Stefan Rehart³, Angela Lehr⁴, Ulf Müller-Ladner⁵ and Elena Neumann⁶, ¹Internal Medicine and Rheumatology, Justus-Liebig-University of Gießen, Kerckhoff-Klinik, Bad Nauheim, Germany, ²Department of Internal Medicine III, Endocrinology, Diabetes, Metabolism, Justus-Liebig-University of Giessen, Giessen, Germany, ³Orthopedics and Trauma Surgery, Markus-Hospital, Frankfurt, Germany, ⁴Dept Orthopedics and Trauma Surgery, Markus-Hospital, Frankfurt, Germany, ⁵Department of Internal Medicine and Rheumatology, Justus-Liebig-University of Gießen, Bad Nauheim, Germany, ⁶Department of Internal Medicine and Rheumatology, Justus-Liebig-University of Gießen, Kerckhoff-Klinik, Bad Nauheim, Germany
Background/Purpose: Due to their role in inflammatory metabolic diseases, we hypothesized that free fatty acids (FFA) are also involved in primary inflammatory joint diseases including…
Abstract Number: 2294 • 2012 ACR/ARHP Annual Meeting
The Histone Deacetylase SIRT1 Is Anti-Fibrotic and Mediates Resveratrol Effects
Roberta G. Marangoni¹, Archit Ghosh¹, Jun Wei² and John Varga³, ¹Medicine, Rheumatolgoy, Northwestern University, Feinberg School of Medicine, Chicago, IL, ²Rheumatology Division, Northwestern University, Chicago, IL, ³Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL
Background/Purpose: Fibrosis in scleroderma is associated with increased collagen synthesis driven by TGF-β and associated epigenetic modifications. The Class III histone deacetylase SIRT1 has anticancer…
Abstract Number: 784 • 2012 ACR/ARHP Annual Meeting
Neutralization of Plasminogen Activator Inhibitor-1 Resolves Skin Fibrosis and Vascular Injury in a Murine Model of Human Scleroderma
Raphael Lemaire¹, Tim Burwell¹, Tracy Delaney¹, Cindy Chen², Julie Bakken¹, Lily Cheng¹, Philip Brohawn¹, Isabelle de Mendez³, Dominic Corkill³, Anthony Coyle⁴, Ronald Herbst² and Jane Connor¹, ¹Research, MedImmune LLC, Gaithersburg, MD, ²Respiration, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, MD, ³Research, Medimmune, LLC, Cambridge, England, ⁴Centers for Therapeutic Innovation, Pfizer, Inc., Cambridge (formerly at MedImmune LLC, Gaithersburg, MD, USA), MA
Background/Purpose: Scleroderma is a systemic autoimmune disease in which thrombosis and fibrosis contribute to skin pathology. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of…

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