LRP5 negatively regulates differentiation of monocytes through abrogation of Wnt signalling
Molecular changes involved in cell differentiation are only partially known. Circulating inflammatory cells need to differentiate to perform specialized functions in target tissues. Here, we hypothesized that low-density lipoprotein receptor-related protein 5 (LRP5) is involved, through its particip...
| Authors: | , , |
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| Format: | article |
| Publication Date: | 2014 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:302329 |
| Online Access: | https://ddd.uab.cat/record/302329 https://dx.doi.org/urn:doi:10.1111/jcmm.12190 |
| Access Level: | Open access |
| Summary: | Molecular changes involved in cell differentiation are only partially known. Circulating inflammatory cells need to differentiate to perform specialized functions in target tissues. Here, we hypothesized that low-density lipoprotein receptor-related protein 5 (LRP5) is involved, through its participation in the canonical Wnt/β-catenin signalling, in the differentiation process of monocytic cells. To this aim, we characterized differentiation mechanisms of HL60 cells and primary human monocytes. We show that silencing the LRP5 gene increased differentiation of HL60 cells and human monocytes, suggesting that LRP5 signalling abrogates differentiation. We demonstrate that the mechanisms behind this blockade include sequestration of β-catenin at the cellular membrane, inhibition of the Wnt signalling and increase of apoptosis. We further demonstrate the involvement of LRP5 and the Wnt/β-catenin signalling in the process because cellular differentiation can be rescued by the addition of downstream Wnt target genes to the monocytic cells. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. |
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