Abstract
In this paper we reviewed and updated current views on the cellular and molecular mechanisms of gastric and esophageal ulcer healing. Gastric ulcer healing encompasses inflammation, cell proliferation, epithelial regeneration, gland reconstruction, formation of granulation tissue, neovascularization (new blood vessel formation), interactions between various cells and the matrix and tissue remodeling, resulting in scar formation. All these events are controlled by the cytokines and growth factors, GI hormones including gastrin , CCK, and orexigenic peptides such as ghrelin, orexin-A and obestatin as well as Cox2 generated prostaglandins. These growth factors and hormones trigger cell proliferation, migration, and survival utilizing Ras, MAPK, PI-3K/AKT, PLC-γ and Rho/Rac/actin signaling pathways. Hypoxia triggers activation of some of these genes (e.g., VEGF) via hypoxia inducible factor (HIF). Growth factors: EGF, HGF, IGF-1, their receptors and Cox2 are important for epithelial cell proliferation, migration, re-epithelialization and regeneration of gastric glands during gastric ulcer healing. Serum response factor (SRF) is also essential for re-epithelialization and muscle restoration. VEGF, bFGF, angiopoietins, nitric oxide, endothelin, prostaglandins and metalloproteinases are important for angiogenesis, vascular remodeling and mucosal regeneration within gastric ulcer scar. SRF is critical limiting factor for VEGF-induced angiogenesis. Esophageal ulcer healing follows similar pattern to gastric ulcer, but KGF and its receptor are the key players in regeneration of the epithelium. In addition to local mucosal cells from viable mucosa bordering necrosis, circulating bone marrow derived stem and progenitor cells are potentially important for ulcer healing, contributing to the regeneration of epithelial and connective tissue components and neovascularization.
Keywords: Ulcer healing, growth factors, re-epithelialization, granulation tissue, angiogenesis, neovascularization, cytokines, prostaglandins, MAPK, hypoxia
Current Medicinal Chemistry
Title: Molecular Mechanisms of Epithelial Regeneration and Neovascularization During Healing of Gastric and Esophageal Ulcers
Volume: 19 Issue: 1
Author(s): A. S. Tarnawski and A. Ahluwalia
Affiliation:
Keywords: Ulcer healing, growth factors, re-epithelialization, granulation tissue, angiogenesis, neovascularization, cytokines, prostaglandins, MAPK, hypoxia
Abstract: In this paper we reviewed and updated current views on the cellular and molecular mechanisms of gastric and esophageal ulcer healing. Gastric ulcer healing encompasses inflammation, cell proliferation, epithelial regeneration, gland reconstruction, formation of granulation tissue, neovascularization (new blood vessel formation), interactions between various cells and the matrix and tissue remodeling, resulting in scar formation. All these events are controlled by the cytokines and growth factors, GI hormones including gastrin , CCK, and orexigenic peptides such as ghrelin, orexin-A and obestatin as well as Cox2 generated prostaglandins. These growth factors and hormones trigger cell proliferation, migration, and survival utilizing Ras, MAPK, PI-3K/AKT, PLC-γ and Rho/Rac/actin signaling pathways. Hypoxia triggers activation of some of these genes (e.g., VEGF) via hypoxia inducible factor (HIF). Growth factors: EGF, HGF, IGF-1, their receptors and Cox2 are important for epithelial cell proliferation, migration, re-epithelialization and regeneration of gastric glands during gastric ulcer healing. Serum response factor (SRF) is also essential for re-epithelialization and muscle restoration. VEGF, bFGF, angiopoietins, nitric oxide, endothelin, prostaglandins and metalloproteinases are important for angiogenesis, vascular remodeling and mucosal regeneration within gastric ulcer scar. SRF is critical limiting factor for VEGF-induced angiogenesis. Esophageal ulcer healing follows similar pattern to gastric ulcer, but KGF and its receptor are the key players in regeneration of the epithelium. In addition to local mucosal cells from viable mucosa bordering necrosis, circulating bone marrow derived stem and progenitor cells are potentially important for ulcer healing, contributing to the regeneration of epithelial and connective tissue components and neovascularization.
Export Options
About this article
Cite this article as:
S. Tarnawski A. and Ahluwalia A., Molecular Mechanisms of Epithelial Regeneration and Neovascularization During Healing of Gastric and Esophageal Ulcers, Current Medicinal Chemistry 2012; 19 (1) . https://dx.doi.org/10.2174/092986712803414088
DOI https://dx.doi.org/10.2174/092986712803414088 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Relevance of Nutritional Antioxidants in Metabolic Syndrome, Ageing and Cancer: Potential for Therapeutic Targeting
Infectious Disorders - Drug Targets The Value of Low-dose Prospective Dual-energy Computed Tomography with Iodine Mapping in the Diagnosis of Gastric Cancer
Current Medical Imaging Dipeptidyl Peptidase IV Inhibitors: A New Paradigm in Type 2 Diabetes Treatment
Current Drug Targets Meet Our Associate Editorial Board Member
Current Pharmaceutical Biotechnology Current Scenario of Acridine Hybrids with Anticancer Potential
Current Topics in Medicinal Chemistry Patented Applications of Gene Silencing in Plants: Manipulation of Traits and Phytopathogen Resistance
Recent Patents on DNA & Gene Sequences Nitrate and Nitrite Removal from Wastewater using Algae
Current Biotechnology Synthesis and Biological Evaluation of New Piperazine Substituted 3, 5-Diarylisoxazolines
Current Organic Synthesis The Role of ABC Transporters in Protecting Cells from Bilirubin Toxicity
Current Pharmaceutical Design Pharmacogenetics of Childhood Acute Lymphoblastic Leukemia
Current Pharmacogenomics Current and Future Drugs for Appetite Regulation and Obesity Treatment
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Bergenin - A Biologically Active Scaffold: Nanotechnological Perspectives
Current Topics in Medicinal Chemistry Development of Peptides as Potential Drugs for Cancer Therapy
Current Pharmaceutical Design Synthesis, Characterization, Biological Activity and Voltammetric Behavior and Determination of Cefaclor Metal Complexes
Current Analytical Chemistry HOXB7 and Hsa-miR-222 as the Potential Therapeutic Candidates for Metastatic Colorectal Cancer
Recent Patents on Anti-Cancer Drug Discovery Magainin-Related Peptides Stimulate Insulin-Release and Improve Glucose Tolerance in High Fat Fed Mice
Protein & Peptide Letters MMP Inhibitors in Cardiac Diseases: An Update
Recent Patents on Cardiovascular Drug Discovery The Discrepancy between Gross Features and Chemical Compositions in Gallbladder Stone: A Descriptive Single Center Study in the United Arab Emirates
New Emirates Medical Journal Safety of One-week, First-line, Standard Triple Therapy for Helicobacter pylori Eradication in a Japanese Population
Current Drug Safety Recent Progress in the Development of Small Molecule c-Met Inhibitors
Current Topics in Medicinal Chemistry