Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases
Thomas A. Wynn
Thomas A. Wynn
Published March 1, 2007
Citation Information: J Clin Invest. 2007;117(3):524-529. https://doi.org/10.1172/JCI31487.
View: Text | PDF
Review Series

Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases

  • Text
  • PDF
Abstract

Fibroproliferative diseases, including the pulmonary fibroses, systemic sclerosis, liver cirrhosis, cardiovascular disease, progressive kidney disease, and macular degeneration, are a leading cause of morbidity and mortality and can affect all tissues and organ systems. Fibrotic tissue remodeling can also influence cancer metastasis and accelerate chronic graft rejection in transplant recipients. Nevertheless, despite its enormous impact on human health, there are currently no approved treatments that directly target the mechanism(s) of fibrosis. The primary goals of this Review series on fibrotic diseases are to discuss some of the major fibroproliferative diseases and to identify the common and unique mechanisms of fibrogenesis that might be exploited in the development of effective antifibrotic therapies.

Authors

Thomas A. Wynn

×

Figure 1

Outcomes of wound healing: tissue regeneration or fibrosis.

Options: View larger image (or click on image) Download as PowerPoint
Outcomes of wound healing: tissue regeneration or fibrosis.
Following ti...
Following tissue injury, epithelial and/or endothelial cells release inflammatory mediators that initiate an antifibrinolytic-coagulation cascade, which triggers blood clot formation. This is followed by an inflammatory and proliferative phase, when leukocytes are recruited and then activated and induced to proliferate by chemokines and growth factors. The activated leukocytes secrete profibrotic cytokines such as IL-13 and TGF-β. Stimulated epithelial cells, endothelial cells, and myofibroblasts also produce MMPs, which disrupt the basement membrane, and additional cytokines and chemokines that recruit and activate neutrophils, macrophages, T cells, B cells, and eosinophils, important components of reparative tissue. The activated macrophages and neutrophils clean up tissue debris, dead cells, and invading organisms. Shortly after the initial inflammatory phase, myofibroblasts produce ECM components, and endothelial cells form new blood vessels. The myofibroblasts can be derived from local mesenchymal cells, recruited from the bone marrow (where they are known as fibrocytes), or derived by EMT. In the subsequent remodeling and maturation phase, the activated myofibroblasts stimulate wound contraction. Collagen fibers also become more organized, blood vessels are restored to normal, scar tissue is eliminated, and epithelial and/or endothelial cells divide and migrate over the basal layers to regenerate the epithelium or endothelium, respectively, restoring the damaged tissue to its normal appearance. However, in the case of chronic wounds, the normal healing process is disrupted. Persistent inflammation, tissue necrosis, and infection lead to chronic myofibroblast activation and excessive accumulation of ECM components, which promotes the formation of a permanent fibrotic scar.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts