Abstract
Pathogenic mechanisms involved in fibrosis of various organs share many common features. Myofibroblasts are thought to play a major role in fibrosis through excessive deposition of extracellular matrix during wound healing processes. Myofibroblasts are observed in fibrotic lesions, and whereas these derive from the hepatic stellate cells in liver, in lung they appear to originate from fibroblasts. The source of these fibroblasts has been the object of numerous studies over the recent years and points towards multiple sources. First of all, resident fibroblasts are thought to differentiate into the more contractile myofibroblasts, secreting many extracellular matrix proteins. Secondly, the epithelial to mesenchymal transition (EMT) of epithelial cells may also account for increased numbers of fibroblasts, though in vivo evidence in patient tissue.is still scarce. Thirdly, the enigmatic fibrocytes, stemming from the bone marrow, may also account for increasing numbers of fibroblasts in fibrotic lesions. These pathogenic processes are further augmented by the generation of so-called alternatively activated macrophages, which have direct and indirect effects on myofibroblast accumulation and collagen deposition. TGFβ, which is produced predominantly by macrophages, plays a central role in all these processes by inducing EMT, driving differentiation of fibrocytes, and differentiation towards myofibroblasts.
This review describes the potential origins and roles of these fibrotic cells in the lung and discusses models to study these cells in vitro. These models offer innovative approaches in target and drug discovery, aiming to uncover novel therapeutic targets that regulate the profibrotic phenotype of these cells.
Keywords: Fibrosis, IPF, EMT, epithelial cell, fibroblasts, fibrocytes, macrophages, TGFβ, Myofibroblasts, collagen.
Current Pharmaceutical Design
Title:Cellular Players in Lung Fibrosis
Volume: 18 Issue: 27
Author(s): Annemarie N. Lekkerkerker, Jamil Aarbiou, Thomas van Es and Richard A.J. Janssen
Affiliation:
Keywords: Fibrosis, IPF, EMT, epithelial cell, fibroblasts, fibrocytes, macrophages, TGFβ, Myofibroblasts, collagen.
Abstract: Pathogenic mechanisms involved in fibrosis of various organs share many common features. Myofibroblasts are thought to play a major role in fibrosis through excessive deposition of extracellular matrix during wound healing processes. Myofibroblasts are observed in fibrotic lesions, and whereas these derive from the hepatic stellate cells in liver, in lung they appear to originate from fibroblasts. The source of these fibroblasts has been the object of numerous studies over the recent years and points towards multiple sources. First of all, resident fibroblasts are thought to differentiate into the more contractile myofibroblasts, secreting many extracellular matrix proteins. Secondly, the epithelial to mesenchymal transition (EMT) of epithelial cells may also account for increased numbers of fibroblasts, though in vivo evidence in patient tissue.is still scarce. Thirdly, the enigmatic fibrocytes, stemming from the bone marrow, may also account for increasing numbers of fibroblasts in fibrotic lesions. These pathogenic processes are further augmented by the generation of so-called alternatively activated macrophages, which have direct and indirect effects on myofibroblast accumulation and collagen deposition. TGFβ, which is produced predominantly by macrophages, plays a central role in all these processes by inducing EMT, driving differentiation of fibrocytes, and differentiation towards myofibroblasts.
This review describes the potential origins and roles of these fibrotic cells in the lung and discusses models to study these cells in vitro. These models offer innovative approaches in target and drug discovery, aiming to uncover novel therapeutic targets that regulate the profibrotic phenotype of these cells.
Export Options
About this article
Cite this article as:
N. Lekkerkerker Annemarie, Aarbiou Jamil, van Es Thomas and A.J. Janssen Richard, Cellular Players in Lung Fibrosis, Current Pharmaceutical Design 2012; 18 (27) . https://dx.doi.org/10.2174/138161212802430396
DOI https://dx.doi.org/10.2174/138161212802430396 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Role of Matrix Gla Protein (MGP) in Vascular Calcification
Current Medicinal Chemistry Pleuroscopy Early Experience in the Exudative Pleural Effusion of Unknown Etiology
Current Respiratory Medicine Reviews P2X Receptors and Inflammation
Current Medicinal Chemistry Adenosine and the Auditory System
Current Neuropharmacology Depression in Coronary Heart Disease Patients: Etiological and Screening Issues
Current Psychiatry Reviews The Etiology of Hypertension in the Metabolic Syndrome Part Three: The Regulation and Dysregulation of Blood Pressure
Current Vascular Pharmacology Acute Coronary Syndrome and its Antithrombotic Treatment: Focus on Aspirin and Clopidogrel Resistance
Current Vascular Pharmacology Rheumatoid Arthritis: An Evolutionary Force in Biologics
Current Pharmaceutical Design Prevalence and Factors Associated With Low Aerobic Performance Levels in Adolescents: A Systematic Review
Current Pediatric Reviews Diffuse Large B-Cell Lymphoma with Involvement of the Chest Wall
Current Respiratory Medicine Reviews Frequency of Cardiac Arrhythmias in Children with Cardiological Consulting and Containing Electrocardiogram
Cardiovascular & Hematological Disorders-Drug Targets Management of Blood Pressure and Heart Rate in Acute Decompensated Heart Failure with Volume Overload
Current Pharmaceutical Design The Sphingolipid Rheostat: A Potential Target for Improving Pancreatic Islet Survival and Function
Endocrine, Metabolic & Immune Disorders - Drug Targets Cost of Atrial Fibrillation: Invasive vs Non-Invasive Management in 2012
Current Cardiology Reviews Editorial [ Diagnosing and Treating Pleural Effusions: The Good, the Bad and the Ugly! ]
Current Respiratory Medicine Reviews Mechanisms of Enhanced Vasoconstriction in the Mouse Model of Atherosclerosis: the Beneficial Effects of Sildenafil
Current Pharmaceutical Biotechnology Clinical Use of Intracoronary Gene Transfer of Fibroblast Growth Factor for Coronary Artery Disease
Current Gene Therapy A Novel Treatment Strategy for Sepsis and Septic Shock Based on the Interactions between Prostanoids, Nitric Oxide, and 20-Hydroxyeicosatetraenoic Acid
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry SIRT1 as a Novel Potential Treatment Target for Vascular Aging and Age-Related Vascular Diseases
Current Molecular Medicine Ruthenium as an Effective Nitric Oxide Scavenger
Current Topics in Medicinal Chemistry