LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes

Immunology and Cell Biology
Maria Borrell-PagesLina Badimon

Abstract

Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 w...Continue Reading

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Citations

Jan 8, 2016·Journal of Molecular and Cellular Cardiology·Yonggang Ma
Dec 17, 2015·Journal of Molecular and Cellular Cardiology·M Borrell-PagesL Badimon
Oct 6, 2016·Basic Research in Cardiology·M Borrell-PagesL Badimon
Feb 18, 2017·Current Opinion in Hematology·Lina Badimon, Maria Borrell-Pages
Apr 19, 2017·Experimental Dermatology·Albert DuvetorpOliver Seifert
Dec 17, 2017·Pharmacological Reviews·Sébastien FoulquierW Matthijs Blankesteijn
Apr 30, 2020·Signal Transduction and Targeted Therapy·Xuemin HeJian-Xing Ma
Aug 17, 2019·Frontiers in Immunology·Elizabeth S MalsinCara J Gottardi
Sep 30, 2020·Cardiovascular Research·Lina BadimonMaria Borrell-Pages

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