Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway

Guido Carpino, Valerio Nobili, Anastasia Renzi, Cristiano De Stefanis, Laura Stronati, Antonio Franchitto, Anna Alisi, Paolo Onori, Rita De Vito, Gianfranco Alpini, Eugenio Gaudio

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.
Original languageEnglish
Article numbere0157246
Pages (from-to)-
JournalPLoS One
Volume11
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Carpino, G., Nobili, V., Renzi, A., De Stefanis, C., Stronati, L., Franchitto, A., Alisi, A., Onori, P., De Vito, R., Alpini, G., & Gaudio, E. (2016). Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway. PLoS One, 11(6), -. [e0157246]. https://doi.org/10.1371/journal.pone.0157246