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
-
Tools and Procedures for Ex Vivo Vein Arterialization, Preconditioning and Tissue Engineering: A Step Forward to Translation to Combat the Consequences of Vascular Graft Remodeling
Recent Patents on Cardiovascular Drug Discovery Integrin α4β7 Antagonists: Activities, Mechanisms of Action and Therapeutic Prospects
Current Immunology Reviews (Discontinued) Antiplatelet Therapy in Children: Why So Different from Adults’?
Current Pharmaceutical Design Hemodynamic Regulation of Metallopeptidases within the Vasculature
Protein & Peptide Letters Bioconversion of Isoflavones into Bioactive Equol: State of the Art
Recent Patents on Food, Nutrition & Agriculture An Insight of Novel Pharmacological Therapies in Hypertrophic Cardiomyopathy
Medicinal Chemistry Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension
Current Pharmaceutical Design The Role of VE-cadherin in Blood-brain Barrier Integrity Under Central Nervous System Pathological Conditions
Current Neuropharmacology Lung Structural Changes in Chronic Obstructive Pulmonary Diseases
Current Drug Targets - Inflammation & Allergy The Mechanism of Action of Praziquantel: Can New Drugs Exploit Similar Mechanisms?
Current Medicinal Chemistry Anti-Selectin Therapy for the Treatment of Inflammatory Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Leptin as a Novel Therapeutic Target for Immune Intervention
Current Drug Targets - Inflammation & Allergy Cancer Therapeutics-Related Cardiovascular Complications. Mechanisms, Diagnosis and Treatment
Current Pharmaceutical Design Editorial (Thematic Issue: Pharmacologic Strategies with Afterload Reduction in Low Cardiac Output Syndrome After Pediatric Cardiac Surgery)
Current Vascular Pharmacology Mycobacterium tuberculosis DNA Gyrase as a Target for Drug Discovery
Infectious Disorders - Drug Targets Cellular Cardiomyoplasty – Challenges of a New Era
Current Tissue Engineering (Discontinued) Potential Deployment of Angiotensin I Converting Enzyme Inhibitors and of Angiotensin II Type 1 and Type 2 Receptor Blockers in Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Chloride Channels − New Targets for the Prevention of Stroke
Current Vascular Pharmacology Potential Role of Endothelin in Early Vascular Aging
Current Hypertension Reviews The CNS Melanocortin System: A Biological Weapon Against the Threat of Obesity
Current Medicinal Chemistry - Central Nervous System Agents