Abstract
Idiopathic Pulmonary Fibrosis (IPF) is characterized by injury and loss of lung epithelial cells, accumulation of fibroblasts/myofibroblasts and abnormal remodeling of the lung parenchyma. The prognosis for IPF patients is poor and current therapies are largely ineffective in preventing respiratory failure. Current therapeutic approaches target epithelial cell replacement, manipulation of fibroblasts/myofibroblasts, modulation of procoagulant/fibrinolytic activities, cytokine and growth factor production, angiogenesis, and reduction of oxidative stress. Myofibroblasts are the primary effector cells in fibrosis. These cells may be derived by the activation and proliferation of resident lung fibroblasts, from epithelialmesenchymal transition (EMT), or through recruitment of circulating fibrocytes. Transforming growth factor β (TGFβ) is a profibrotic factor that increases fibroblast proliferation, stimulates the synthesis and deposition of connective tissue, and inhibits connective tissue breakdown. TGFβ acts through the promoter of the type 1 collagen gene causing increased collagen synthesis. In addition, TGFβ induces EMT in alveolar epithelial cells (AECs) in vitro and in vivo. AECs exhibit substantial plasticity and may serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. Therapeutic interventions interfering with the pathways that lead to myofibroblast expansion and AEC apoptosis should be of considerable benefit in the treatment of IPF. This review will focus on the critical role of TGFβ on AECs EMT and myofibroblasts in the development of fibrosis.
Keywords: Anti-fibrotic agents, lung fibrosis, fibrocytes, pathogenesis, myofibroblast, Transforming growth factor β, treatment
Current Medicinal Chemistry
Title: Recent Advances in Molecular Targets and Treatment of Idiopathic Pulmonary Fibrosis: Focus on TGFβ Signaling and the Myofibroblast
Volume: 16 Issue: 11
Author(s): M. Gharaee-Kermani, B. Hu, S. H. Phan and M. R. Gyetko
Affiliation:
Keywords: Anti-fibrotic agents, lung fibrosis, fibrocytes, pathogenesis, myofibroblast, Transforming growth factor β, treatment
Abstract: Idiopathic Pulmonary Fibrosis (IPF) is characterized by injury and loss of lung epithelial cells, accumulation of fibroblasts/myofibroblasts and abnormal remodeling of the lung parenchyma. The prognosis for IPF patients is poor and current therapies are largely ineffective in preventing respiratory failure. Current therapeutic approaches target epithelial cell replacement, manipulation of fibroblasts/myofibroblasts, modulation of procoagulant/fibrinolytic activities, cytokine and growth factor production, angiogenesis, and reduction of oxidative stress. Myofibroblasts are the primary effector cells in fibrosis. These cells may be derived by the activation and proliferation of resident lung fibroblasts, from epithelialmesenchymal transition (EMT), or through recruitment of circulating fibrocytes. Transforming growth factor β (TGFβ) is a profibrotic factor that increases fibroblast proliferation, stimulates the synthesis and deposition of connective tissue, and inhibits connective tissue breakdown. TGFβ acts through the promoter of the type 1 collagen gene causing increased collagen synthesis. In addition, TGFβ induces EMT in alveolar epithelial cells (AECs) in vitro and in vivo. AECs exhibit substantial plasticity and may serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. Therapeutic interventions interfering with the pathways that lead to myofibroblast expansion and AEC apoptosis should be of considerable benefit in the treatment of IPF. This review will focus on the critical role of TGFβ on AECs EMT and myofibroblasts in the development of fibrosis.
Export Options
About this article
Cite this article as:
Gharaee-Kermani M., Hu B., Phan H. S. and Gyetko R. M., Recent Advances in Molecular Targets and Treatment of Idiopathic Pulmonary Fibrosis: Focus on TGFβ Signaling and the Myofibroblast, Current Medicinal Chemistry 2009; 16 (11) . https://dx.doi.org/10.2174/092986709787846497
DOI https://dx.doi.org/10.2174/092986709787846497 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Delivery of Intracellular-Acting Biologics in Pro-Apoptotic Therapies
Current Pharmaceutical Design Pharmacology of Cyclic Peptides: Vancomycin and Oxytocin as Paradigms
Protein & Peptide Letters The Updated Role of Oxidative Stress in Subarachnoid Hemorrhage
Current Drug Delivery Insights into the Structure of Protein by Vibrational Spectroscopy
Current Pharmaceutical Analysis Message from the Editor-in-Chief:
CNS & Neurological Disorders - Drug Targets Thiazole Compounds as Antiviral Agents: An Update
Medicinal Chemistry Integrins: Novel Therapeutic Targets for Cardiovascular Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry New Insight into P-Glycoprotein as a Drug Target
Anti-Cancer Agents in Medicinal Chemistry Gestational Exposure to Variable Stressors Produces Decrements in Cognitive and Neural Development of Juvenile Male and Female Rats
Current Topics in Medicinal Chemistry Malaria in Children - Prevention and Management
Infectious Disorders - Drug Targets Application of Nano- and Micro-Particles on the Topical Therapy of Skin-Related Immune Disorders
Current Pharmaceutical Design The Role of Nitric Oxide (NO) in Control of LHRH Release that Mediates Gonadotropin Release and Sexual Behavior
Current Pharmaceutical Design A Comprehensive Study of miRNAs in Parkinson’s Disease: Diagnostics and Therapeutic Approaches
CNS & Neurological Disorders - Drug Targets Pharmacogenetics of Anti-Inflammatory Therapy in Asthma: Corticosteroids and Leukotriene Antagonists
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment
Current Neuropharmacology Influence of a Novel Inhibitor (UM8190) of Prolylcarboxypeptidase (PRCP) on Appetite and Thrombosis
Current Medicinal Chemistry Recent Patents on Oral Insulin Delivery
Recent Patents on Drug Delivery & Formulation Nigella sativa and Cancer: A Review Focusing on Breast Cancer, Inhibition of Metastasis and Enhancement of Natural Killer Cell Cytotoxicity
Current Pharmaceutical Biotechnology Nitric Oxide and its Derivatives Containing Nasal Spray and Inhalation Therapy for the Treatment of COVID-19
Current Pharmaceutical Design Disruption of Circadian Rhythms and Sleep in Critical Illness and its Impact on the Development of Delirium
Current Pharmaceutical Design