![conference banner](/images/conference-banner.jpeg)
Abstract
Persistent exposure of biliary epithelial cells (i.e., cholangiocytes) to diverse factors such as disordered immunity, genetic alterations, ischemia, toxic compounds and/or infectious agents leads to a chronic portal inflammatory response which eventually progresses to biliary fibrosis. This stage is characterized by increased production and deposition of scar-forming extracellular matrix proteins (ECM), in particular fibrillar collagen types I and III, but including other ECM constituents such as elastin and fibrillin-1, both components of elastic fibers. The major cellular mediators responsible for collagen deposition are activated hepatic stellate cells (HSCs) and to a lesser extent, portal myofibroblasts, which are activated by soluble inflammatory mediators (i.e., cytokines, growth factors) and extracellular matrix components. Unless the underlying cause of biliary injury can be effectively treated, these processes may ultimately lead to decompensated cirrhosis and can also provide ideal microenvironments for the development and growth of primary tumors. Recent evidence indicates that fibrosis is a dynamic and potentially reversible process. As the curative options for most chronic biliary diseases remain limited to transplantation, there is an urgent need to clarify the molecular pathways involved in the development of biliary fibrosis and identify new therapeutic targets. In this review we describe the cellular and molecular regulators that orchestrate the cholangiocyte /myofibroblast cross-talk and identify the signaling processes that are most promising for therapeutic targeting.
Keywords: Biliary fibrosis, ductular reaction, myofibroblast, reactive cholangiocyte, therapeutic targets.
Current Drug Targets
Title:New Advances in the Molecular Mechanisms Driving Biliary Fibrosis and Emerging Molecular Targets
Volume: 18 Issue: 8
Author(s): Alvaro Santos-Laso, Patricia Munoz-Garrido, Maialen Felipe-Agirre, Luis Bujanda, Jesus M. Banales and Maria J. Perugorria*
Affiliation:
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, Paseo del Dr. Begiristain s/n, E-20014, San Sebastian,Spain
Keywords: Biliary fibrosis, ductular reaction, myofibroblast, reactive cholangiocyte, therapeutic targets.
Abstract: Persistent exposure of biliary epithelial cells (i.e., cholangiocytes) to diverse factors such as disordered immunity, genetic alterations, ischemia, toxic compounds and/or infectious agents leads to a chronic portal inflammatory response which eventually progresses to biliary fibrosis. This stage is characterized by increased production and deposition of scar-forming extracellular matrix proteins (ECM), in particular fibrillar collagen types I and III, but including other ECM constituents such as elastin and fibrillin-1, both components of elastic fibers. The major cellular mediators responsible for collagen deposition are activated hepatic stellate cells (HSCs) and to a lesser extent, portal myofibroblasts, which are activated by soluble inflammatory mediators (i.e., cytokines, growth factors) and extracellular matrix components. Unless the underlying cause of biliary injury can be effectively treated, these processes may ultimately lead to decompensated cirrhosis and can also provide ideal microenvironments for the development and growth of primary tumors. Recent evidence indicates that fibrosis is a dynamic and potentially reversible process. As the curative options for most chronic biliary diseases remain limited to transplantation, there is an urgent need to clarify the molecular pathways involved in the development of biliary fibrosis and identify new therapeutic targets. In this review we describe the cellular and molecular regulators that orchestrate the cholangiocyte /myofibroblast cross-talk and identify the signaling processes that are most promising for therapeutic targeting.
Export Options
About this article
Cite this article as:
Santos-Laso Alvaro, Munoz-Garrido Patricia, Felipe-Agirre Maialen, Bujanda Luis, Banales M. Jesus and Perugorria J. Maria*, New Advances in the Molecular Mechanisms Driving Biliary Fibrosis and Emerging Molecular Targets, Current Drug Targets 2017; 18 (8) . https://dx.doi.org/10.2174/1389450116666150427155035
DOI https://dx.doi.org/10.2174/1389450116666150427155035 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response, and/or therapy ...read more
Therapeutic Chemical and RNA Design with Artificial Intelligence
Computer-Aided Drug Design (CADD) has emerged as a fundamental component of modern drug discovery. Molecular docking facilitates virtual screening on a large scale through structural simulations. However, traditional CADD approaches face significant limitations, as they can only screen known compounds from existing libraries. PubChem, as the most widely used chemical ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
Related Articles
-
Congenital Scoliosis (Mini-review)
Current Pediatric Reviews NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment
Current Medicinal Chemistry What Does a Pediatrician Need to Know About Chronic Diarrhea?
Current Pediatric Reviews Insight γ-Secretase: Structure, Function, and Role in Alzheimer’s Disease
Current Drug Targets Orally Administrated Small Molecule Drugs with Intestine Targeted Profile: Recent Development and Prospects
Current Medicinal Chemistry Saturation of the Human Phenome
Current Genomics Personalized and Regenerative Medicine for Liver Diseases
Current Stem Cell Research & Therapy Notch Signaling in Cardiovascular Disease and Calcification
Current Cardiology Reviews Targeting Notch as a Therapeutic Approach for Human Malignancies
Current Pharmaceutical Design Unfoldomics of Human Genetic Diseases: Illustrative Examples of Ordered and Intrinsically Disordered Members of the Human Diseasome
Protein & Peptide Letters Renal Development: A Complex Process Dependent on Inductive Interaction
Current Pediatric Reviews Different Generations of Type-B Monoamine Oxidase Inhibitors in Parkinson’s Disease: From Bench to Bedside
Current Neuropharmacology Cell Death and microRNAs in Cholestatic Liver Diseases: Update on Potential Therapeutic Applications
Current Drug Targets Newly Described Mutations of the UNC45A Gene in Infants with Jaundice and Pruritus
Current Pediatric Reviews Autoimmune Hepatitis: A Childhood Disease
Current Pediatric Reviews Nutrition and Growth in Children with Chronic Liver Disease and After Liver Transplantation
Current Nutrition & Food Science Past and Recent Progress of Molecular Imaging Probes for β-Amyloid Plaques in the Brain
Current Medicinal Chemistry Similar Mechanisms Regulated by γ-Secretase are Involved in Both Directions of the Bi-Directional Notch-Delta Signaling Pathway as well as Play a Potential Role in Signaling Events Involving Type 1 Transmembrane Proteins
Current Stem Cell Research & Therapy Current Options for Treatment of End-Stage Liver Disease in Children
Current Pediatric Reviews Recent Developments in Group I Metabotropic Glutamate Receptor Allosteric Modulators for the Treatment of Psychiatric and Neurological Disorders (2014-May 2015)
Current Topics in Medicinal Chemistry