scholarly journals The Low Density Lipoprotein Receptor-1, LRP1, Interacts with the Human Frizzled-1 (HFz1) and Down-regulates the Canonical Wnt Signaling Pathway

2004 ◽  
Vol 279 (17) ◽  
pp. 17535-17542 ◽  
Author(s):  
Alona Zilberberg ◽  
Abraham Yaniv ◽  
Arnona Gazit
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Low Density Lipoprotein ◽  
Wnt Signaling Pathway ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Canonical Wnt

scholarly journals Macrophage LRP1 Promotes Diet-Induced Hepatic Inflammation and Metabolic Dysfunction by Modulating Wnt Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Dianaly T. Au ◽  
Mary Migliorini ◽  
Dudley K. Strickland ◽  
Selen C. Muratoglu
Keyword(s):  
Insulin Resistance ◽  
Wnt Signaling ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Hepatic Inflammation ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

Hepatic inflammation is associated with the development of insulin resistance, which can perpetuate the disease state and may increase the risk of metabolic syndrome and diabetes. Despite recent advances, mechanisms linking hepatic inflammation and insulin resistance are still unclear. The low-density lipoprotein receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is highly expressed in macrophages, adipocytes, hepatocytes, and vascular smooth muscle cells. To investigate the potential role of macrophage LRP1 in hepatic inflammation and insulin resistance, we conducted experiments using macrophage-specific LRP1-deficient mice (macLRP1−/−) generated on a low-density lipoprotein receptor knockout (LDLR−/−) background and fed a Western diet. LDLR−/−; macLRP1−/− mice gained less body weight and had improved glucose tolerance compared to LDLR−/− mice. Livers from LDLR−/−; macLRP1−/− mice displayed lower levels of gene expression for several inflammatory cytokines, including Ccl3, Ccl4, Ccl8, Ccr1, Ccr2, Cxcl9, and Tnf, and reduced phosphorylation of GSK3α and p38 MAPK proteins. Furthermore, LRP1-deficient peritoneal macrophages displayed altered cholesterol metabolism. Finally, circulating levels of sFRP-5, a potent anti-inflammatory adipokine that functions as a decoy receptor for Wnt5a, were elevated in LDLR−/−; macLRP1−/− mice. Surface plasmon resonance experiments revealed that sFRP-5 is a novel high affinity ligand for LRP1, revealing that LRP1 regulates levels of this inhibitor of Wnt5a-mediated signaling. Collectively, our results suggest that LRP1 expression in macrophages promotes hepatic inflammation and the development of glucose intolerance and insulin resistance by modulating Wnt signaling.

scholarly journals Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond

2021 ◽  
Vol 9 ◽  
Author(s):  
Wonyoung Jeong ◽  
Eek-hoon Jho
Keyword(s):  
Wnt Signaling ◽  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Related Protein ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Receptor Related Protein

Wnt signaling plays crucial roles in development and tissue homeostasis, and its dysregulation leads to various diseases, notably cancer. Wnt/β-catenin signaling is initiated when the glycoprotein Wnt binds to and forms a ternary complex with the Frizzled and low-density lipoprotein receptor-related protein 5/6 (LRP5/6). Despite being identified as a Wnt co-receptor over 20 years ago, the molecular mechanisms governing how LRP6 senses Wnt and transduces downstream signaling cascades are still being deciphered. Due to its role as one of the main Wnt signaling components, the dysregulation or mutation of LRP6 is implicated in several diseases such as cancer, neurodegeneration, metabolic syndrome and skeletal disease. Herein, we will review how LRP6 is activated by Wnt stimulation and explore the various regulatory mechanisms involved. The participation of LRP6 in other signaling pathways will also be discussed. Finally, the relationship between LRP6 dysregulation and disease will be examined in detail.

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