Abstract
Liver fibrosis is a pathological consequence of chronic liver diseases and results from the progressive accumulation of altered extracellular matrix, highly enriched in type I and III fibrillar collagens. In advanced stages, fibrosis leads to cirrhosis, defined by abnormal liver architecture and altered vascularization. Clinical consequences of cirrhosis are failure in the synthetic function of the liver, portal hypertension, high susceptibility to infection and high risk to develop hepatocellular carcinoma (HCC). The TGF- family of cytokines plays essential roles in many cellular processes, including growth inhibition, cell migration and invasion, extracellular matrix remodelling and immune suppression, being involved in the maintenance of tissue homeostasis. However, TGF-s are often continuously overexpressed in disease states, such as fibrosis, inflammation and cancer, and they play pivotal roles in the sequence of events leading to end-stage of chronic liver diseases. Reactive oxygen species (ROS) are critical intermediates in liver physiology and pathology. When the equilibrium between ROS generation and the antioxidant defence of the cell is disrupted, it results in an oxidative stress process. The NADPH oxidase (NOX) family has emerged in the last years as important source of ROS in liver pathologies. Interestingly, NOXes mediate TGF- actions in liver cells, such as regulation of hepatocyte growth and death, as well as activation of hepatic stellate cells to myofibroblasts, key executers of the fibrotic process. In this review we will update the relevant and differential roles of NOX isoforms during liver fibrosis and hepatocarcinogenesis, their cross-talk with the TGF- pathway and their potential as therapeutic targets for these diseases.
Keywords: NADPH oxidases, chronic liver diseases, liver cancer, TGF-beta, NOX1, NOX4, NOX2.
Current Pharmaceutical Design
Title:Cross-Talk Between TGF-β and NADPH Oxidases During Liver Fibrosis and Hepatocarcinogenesis
Volume: 21 Issue: 41
Author(s): Eva Crosas-Molist, Esther Bertran and Isabel Fabregat
Affiliation:
Keywords: NADPH oxidases, chronic liver diseases, liver cancer, TGF-beta, NOX1, NOX4, NOX2.
Abstract: Liver fibrosis is a pathological consequence of chronic liver diseases and results from the progressive accumulation of altered extracellular matrix, highly enriched in type I and III fibrillar collagens. In advanced stages, fibrosis leads to cirrhosis, defined by abnormal liver architecture and altered vascularization. Clinical consequences of cirrhosis are failure in the synthetic function of the liver, portal hypertension, high susceptibility to infection and high risk to develop hepatocellular carcinoma (HCC). The TGF- family of cytokines plays essential roles in many cellular processes, including growth inhibition, cell migration and invasion, extracellular matrix remodelling and immune suppression, being involved in the maintenance of tissue homeostasis. However, TGF-s are often continuously overexpressed in disease states, such as fibrosis, inflammation and cancer, and they play pivotal roles in the sequence of events leading to end-stage of chronic liver diseases. Reactive oxygen species (ROS) are critical intermediates in liver physiology and pathology. When the equilibrium between ROS generation and the antioxidant defence of the cell is disrupted, it results in an oxidative stress process. The NADPH oxidase (NOX) family has emerged in the last years as important source of ROS in liver pathologies. Interestingly, NOXes mediate TGF- actions in liver cells, such as regulation of hepatocyte growth and death, as well as activation of hepatic stellate cells to myofibroblasts, key executers of the fibrotic process. In this review we will update the relevant and differential roles of NOX isoforms during liver fibrosis and hepatocarcinogenesis, their cross-talk with the TGF- pathway and their potential as therapeutic targets for these diseases.
Export Options
About this article
Cite this article as:
Crosas-Molist Eva, Bertran Esther and Fabregat Isabel, Cross-Talk Between TGF-β and NADPH Oxidases During Liver Fibrosis and Hepatocarcinogenesis, Current Pharmaceutical Design 2015; 21 (41) . https://dx.doi.org/10.2174/1381612821666151029112126
DOI https://dx.doi.org/10.2174/1381612821666151029112126 |
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
-
Association of Genetic Polymorphisms of CYP2C9 and VKORC1 with Bleeding Following Warfarin: A Case-Control Study
Current Clinical Pharmacology Association between Apolipoproteins AI and B and Ultrasound Indicators of Carotid Atherosclerosis
Current Vascular Pharmacology Modern Drug Discovery Technologies: Opportunities and Challenges in Lead Discovery
Combinatorial Chemistry & High Throughput Screening Roles of Adrenomedullin in Hypertension and Hypertensive Organ Damage
Current Hypertension Reviews Endothelial Dysfunction and Inflammatory Markers of Vascular Disease
Current Vascular Pharmacology Editorial [Hot Topic: Nitric Oxide and Hydrogen Sulfide - Contribution of Gaseous Messengers to the Cardiovascular Control (Guest Editor: Sona Cacanyiova)]
Current Pharmaceutical Biotechnology The Mechanisms of Gastric Mucosal Injury: Focus on Microvascular Endothelium as a Key Target
Current Medicinal Chemistry Sodium Ion Transporters as New Therapeutic Targets in Heart Failure
Cardiovascular & Hematological Agents in Medicinal Chemistry Treatment of Chronic Hepatitis B: From Research to Clinical Practice Via the Consensus Conferences
Current Pharmaceutical Design PET Imaging of Beta-Adrenoceptors in Human Brain: A Realistic Goal or a Mirage?
Current Pharmaceutical Design Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease
Current Pharmaceutical Design Socioeconomic Position and Type 2 Diabetes Mellitus in Europe 1999- 2009: a Panorama of Inequalities
Current Diabetes Reviews Outline of Proteins and Signaling Pathways Involved in Heart Failure
Current Protein & Peptide Science Design, Synthesis and Biological Evaluation of Benzopyran Derivatives as KATP Channel Openers
Letters in Drug Design & Discovery Vitamin D and Cardiovascular Disease
Current Vascular Pharmacology Impaired Cerebral Autoregulation and Vasomotor Reactivity in Sporadic Alzheimer’s Disease
Current Alzheimer Research Supplementation of Creatine and Ribose Prevents Apoptosis and Right Ventricle Hypertrophy in Hypoxic Hearts
Current Pharmaceutical Design Regulation of Adrenomedullin and its Family Peptide by RAMP System – Lessons from Genetically Engineered Mice
Current Protein & Peptide Science A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress
Cardiovascular & Hematological Disorders-Drug Targets Healthy Diet and Reduction of Chronic Disease Risks of Night Shift Workers
Current Medicinal Chemistry