Back to Search
Start Over
Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway
- Source :
- PLoS ONE, PLoS ONE, Vol 11, Iss 6, p e0157246 (2016)
- Publication Year :
- 2016
- Publisher :
- Public Library of Science, 2016.
-
Abstract
- Non-alcoholic fatty liver disease is one of the most important causes of liver-related morbidity in children. In non-alcoholic fatty liver disease, the activation of liver resident macrophage pool is a central event in the progression of liver injury. The aims of the present study were to evaluate the polarization of liver macrophages and the possible role of Wnt3a production by macrophages in hepatic progenitor cell response in the progression of pediatric nonalcoholic fatty liver disease. 32 children with biopsy-proven non-alcoholic fatty liver disease were included. 20 out of 32 patients were treated with docosahexaenoic acid for 18 months and biopsies at the baseline and after 18 months were included. Hepatic progenitor cell activation, macrophage subsets and Wnt/β-catenin pathway were evaluated by immunohistochemistry and immunofluorescence. Our results indicated that in pediatric non-alcoholic fatty liver disease, pro-inflammatory macrophages were the predominant subset. Macrophage polarization was correlated with Non-alcoholic fatty liver disease Activity Score, ductular reaction, and portal fibrosis; docosahexaenoic acid treatment determined a macrophage polarization towards an anti-inflammatory phenotype in correlation with the reduction of serum inflammatory cytokines, with increased macrophage apoptosis, and with the upregulation of macrophage Wnt3a expression; macrophage Wnt3a expression was correlated with β-catenin phosphorylation in hepatic progenitor cells and signs of commitment towards hepatocyte fate. In conclusion, macrophage polarization seems to have a key role in the progression of pediatric non-alcoholic fatty liver disease; the modulation of macrophage polarization could drive hepatic progenitor cell response by Wnt3a production. © 2016 Carpino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Subjects :
- 0301 basic medicine
Male
Pathology
Steatosis
Biopsy
Anti-Inflammatory Agents
lcsh:Medicine
Pathology and Laboratory Medicine
Pediatrics
Cytopathology
White Blood Cells
0302 clinical medicine
Animal Cells
Non-alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease
hepatic progenitor cell
Medicine and Health Sciences
Macrophage
Phosphorylation
lcsh:Science
Child
Immune Response
beta Catenin
Liver injury
Multidisciplinary
Liver Diseases
Stem Cells
Fatty liver
3. Good health
medicine.anatomical_structure
Liver
Docosahexaenoic acid
Hepatocyte
Disease Progression
030211 gastroenterology & hepatology
Female
Cellular Types
Anatomy
Research Article
Signal Transduction
medicine.medical_specialty
liver
non-alcoholic fatty liver disease
Adolescent
Docosahexaenoic Acids
Kupffer Cells
Immune Cells
Immunology
Macrophage polarization
Surgical and Invasive Medical Procedures
Gastroenterology and Hepatology
Biology
03 medical and health sciences
Signs and Symptoms
Diagnostic Medicine
Wnt3A Protein
medicine
Humans
Progenitor cell
Inflammation
Blood Cells
Macrophages
lcsh:R
Biology and Life Sciences
Cell Biology
Macrophage Activation
medicine.disease
Fibrosis
Fatty Liver
030104 developmental biology
Gene Expression Regulation
Anatomical Pathology
Hepatocytes
lcsh:Q
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....d743df5730d44a26abc3fd73caaa98d0