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
-
Biomarkers in the Evaluation and Management of Idiopathic Pulmonary Fibrosis
Current Topics in Medicinal Chemistry Evaluation of Drug Targeting Strategies and Liposomal Trafficking
Current Pharmaceutical Design Anti-Inflammatory Therapeutic Approaches to Reduce Acute Atherosclerotic Complications
Current Pharmaceutical Biotechnology Lifestyle Changes and Surgical Treatment for Hypertension in the Elderly
Cardiovascular & Hematological Agents in Medicinal Chemistry Protein Kinases as Drug Targets in Human and Animal Diseases
Current Enzyme Inhibition Novelty in Treatment of Pulmonary Fibrosis: Pulmonary Hypertension Drugs and Others
Cardiovascular & Hematological Agents in Medicinal Chemistry ATP-Sensitive K+ Channel Openers: Old Drugs with New Clinical Benefits for the Heart
Current Vascular Pharmacology Diabetic CVD – Soluble Epoxide Hydrolase as A Target
Cardiovascular & Hematological Agents in Medicinal Chemistry Angiotensin Converting Enzyme 2 Activator (DIZE) Modulates Metabolic Profiles in Mice, Decreasing Lipogenesis
Protein & Peptide Letters An Overview of Prospective Drugs for Type 1 and Type 2 Diabetes
Current Drug Targets The Role of Macrophage Migration Inhibitory Factor in Critical Illness
Mini-Reviews in Medicinal Chemistry Exosomal MiR-29a in Cardiomyocytes Induced by Angiotensin II Regulates Cardiac Microvascular Endothelial Cell Proliferation, Migration and Angiogenesis by Targeting VEGFA
Current Gene Therapy C/EBP Transcription Factors in Lung Disease
Current Respiratory Medicine Reviews Transmission Electron Microscopy as Key Technique for the Characterization of Telocytes
Current Stem Cell Research & Therapy Contemporary Management of Hypertension - How to Optimize Therapy
Cardiovascular & Hematological Disorders-Drug Targets Towards a Personalised Approach to Managing Influenza Infections in Infants and Children – Food for Thought and a Note on Oseltamivir
Infectious Disorders - Drug Targets Q Fever Endocarditis
Infectious Disorders - Drug Targets Small Molecules as Anti-TNF Drugs
Current Medicinal Chemistry Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine
Current Medicinal Chemistry Encapsulation of Imatinib in Targeted KIT-5 Nanoparticles for Reducing its Cardiotoxicity and Hepatotoxicity
Anti-Cancer Agents in Medicinal Chemistry