Fibroblasts in fibrosis: novel roles and mediators

被引:745
作者
Kendall, Ryan T. [1 ]
Feghali-Bostwick, Carol A. [1 ]
机构
[1] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA
来源
FRONTIERS IN PHARMACOLOGY | 2014年 / 5卷
关键词
fibroblast; myofibroblast; fibrosis; scleroderma; idiopathic pulmonary fibrosis; extracellular matrix; endostatin; IDIOPATHIC PULMONARY-FIBROSIS; GROWTH-FACTOR-BETA; PROGRESSIVE TUBULOINTERSTITIAL FIBROSIS; SYSTEMIC-SCLEROSIS PATIENTS; INTERSTITIAL LUNG-DISEASE; HEPATIC STELLATE CELLS; SYNTHASE KINASE 3; VITAMIN-D; MESENCHYMAL TRANSITION; COLLAGEN PRODUCTION;
D O I
10.3389/fphar.2014.00123
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Fibroblasts are the most common cell type of the connective tissues found throughout the body and the principal source of the extensive extracellular matrix (ECM) characteristic of these tissues. They are also the central mediators of the pathological fibrotic accumulation of ECM and the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation. The transformation of the fibroblast cell lineage involves classical developmental signaling programs and includes a surprisingly diverse range of precursor cell types most notably, myofibroblasts that are the apex of the fibrotic phenotype. Myofibroblasts display exaggerated ECM production; constitutively secrete and are hypersensitive to chemical signals such as cytokines, chemokines, and growth factors; and are endowed with a contractile apparatus allowing them to manipulate the ECM fibers physically to close open wounds. In addition to ECM production, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. We now recognize many common fibroblast-related features across various physiological and pathological protracted processes. Indeed, a new appreciation has emerged for the role of non-cancerous fibroblast interactions with tumors in cancer progression. Although the predominant current clinical treatments of fibrosis involve non-specific immunosuppressive and anti-proliferative drugs, a variety of potential therapies under investigation specifically target fibroblast biology.
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共 162 条
  • [1] Akt1 Mediates α-Smooth Muscle Actin Expression and Myofibroblast Differentiation via Myocardin and Serum Response Factor
    Abdalla, Maha
    Goc, Anna
    Segar, Lakshman
    Somanath, Payaningal R.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (46) : 33483 - 33493
  • [2] Scleroderma: from cell and molecular mechanisms to disease models
    Abraham, DJ
    Varga, J
    [J]. TRENDS IN IMMUNOLOGY, 2005, 26 (11) : 587 - 595
  • [3] Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis
    Akhmetshina, Alfiya
    Palumbo, Katrin
    Dees, Clara
    Bergmann, Christina
    Venalis, Paulius
    Zerr, Pawel
    Horn, Angelika
    Kireva, Trayana
    Beyer, Christian
    Zwerina, Jochen
    Schneider, Holm
    Sadowski, Anika
    Riener, Marc-Oliver
    MacDougald, Ormond A.
    Distler, Oliver
    Schett, Georg
    Distler, Joerg H. W.
    [J]. NATURE COMMUNICATIONS, 2012, 3
  • [4] Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet
    Akita, Shingo
    Kubota, Koji
    Kobayashi, Akira
    Misawa, Ryosuke
    Shimizu, Akira
    Nakata, Takenari
    Yokoyama, Takahide
    Takahashi, Masafumi
    Miyagawa, Shinichi
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 420 (04) : 743 - 749
  • [5] NOX4/NADPH oxidase expression is increased in pulmonary fibroblasts from patients with idiopathic pulmonary fibrosis and mediates TGFβ1-induced fibroblast differentiation into myofibroblasts
    Amara, Nadia
    Goven, Delphine
    Prost, Fabienne
    Muloway, Rachel
    Crestani, Bruno
    Boczkowski, Jorge
    [J]. THORAX, 2010, 65 (08) : 733 - 738
  • [6] Characteristics and outcomes of patients with sarcoidosis listed for lung transplantation
    Arcasoy, SM
    Christie, JD
    Pochettino, A
    Rosengard, BR
    Blumenthal, NP
    Bavaria, JE
    Kotloff, RM
    [J]. CHEST, 2001, 120 (03) : 873 - 880
  • [7] PITUITARY EXTRACTS AND STEROID-HORMONES IN CONTROL 3T3-CELL GROWTH
    ARMELIN, HA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1973, 70 (09) : 2702 - 2706
  • [8] Pericytes regulate the blood-brain barrier
    Armulik, Annika
    Genove, Guillem
    Mae, Maarja
    Nisancioglu, Maya H.
    Wallgard, Elisabet
    Niaudet, Colin
    He, Liqun
    Norlin, Jenny
    Lindblom, Per
    Strittmatter, Karin
    Johansson, Bengt R.
    Betsholtz, Christer
    [J]. NATURE, 2010, 468 (7323) : 557 - U231
  • [9] Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: A retrospective cohort study and review of the literature
    Arnson, Yoav
    Amital, Howard
    Agmon-Levin, Nancy
    Alon, Danny
    Sanchez-Castanon, Maria
    Lopez-Hoyos, Marcos
    Matucci-Cerinic, Marco
    Szuecs, Gabriella
    Shapira, Yinon
    Szekanecz, Zoltan
    Shoenfeld, Yehuda
    [J]. AUTOIMMUNITY REVIEWS, 2011, 10 (08) : 490 - 494
  • [10] Thrombin Increases Lung Fibroblast Survival while Promoting Alveolar Epithelial Cell Apoptosis via the Endoplasmic Reticulum Stress Marker, CCAAT Enhancer-Binding Homologous Protein
    Atanelishvili, Ilia
    Liang, Jun
    Akter, Tanjina
    Spyropoulos, Demetri D.
    Silver, Richard M.
    Bogatkevich, Galina S.
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2014, 50 (05) : 893 - 902