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
-
Atrial Remodeling and Novel Pharmacological Strategies for Antiarrhythmic Therapy in Atrial Fibrillation
Current Medicinal Chemistry Ethiopathogenesis, Diagnosis and Prevention of Vascular Calcification in End Stage Renal Disease
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Complications Associated with Recombinant Tissue Plasminogen Activator Therapy for Acute Ischaemic Stroke
CNS & Neurological Disorders - Drug Targets Subject Index To Volume 12
Current Pharmaceutical Design Acute Kidney Injury in Pediatric Heart Failure
Current Cardiology Reviews Three Dimensional Echocardiography: Recent Trends in Segmen tation Methods
Current Medical Imaging Continuous Positive Airway Pressure Treatment in Patients with Sleep Apnoea: Does it Really Improve Glucose Metabolism?
Current Diabetes Reviews Current Status of Antiplatelet Therapy in Acute Coronary Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry Inhibitors of Nitric Oxide Synthase: What's up and What's Next?
Current Enzyme Inhibition Free Radical Scanvenging and Antioxidant Effects of Some Anthraquinone Derivatives
Medicinal Chemistry Pain Management in Hematological Patients with Major Organ Dysfunctions and Comorbid Illnesses
Cardiovascular & Hematological Agents in Medicinal Chemistry Emerging Influenza Viruses: Past and Present
Current Molecular Medicine Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction
Current Topics in Medicinal Chemistry NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions
Current Pharmaceutical Design Animal Models of Atherosclerosis Progression: Current Concepts
Current Drug Targets - Cardiovascular & Hematological Disorders Current Status of Lung Ventilation Imaging with Magnetic Resonance Ventilation Scanning Using Aerosolized Contrast Agents
Current Respiratory Medicine Reviews Heparins with Reduced Anti-Coagulant Activity Reduce Myocardial Reperfusion Injury
Recent Patents on Cardiovascular Drug Discovery Cross-Talk between Oxidative Stress and Pro-Inflammatory Cytokines in Acute Pancreatitis: A Key Role for Protein Phosphatases
Current Pharmaceutical Design Mycobacterium w Immunotherapy for Treating Pulmonary Tuberculosis - a Systematic Review
Current Pharmaceutical Design Alpha 1 Anti-Trypsin: One Protein, Many Functions
Current Molecular Medicine