LRP5 negatively regulates differentiation of monocytes through abrogation of Wnt signalling
Por:
Borrell-Pages, M, Romero, JC, Badimon, L
Publicada:
1 feb 2014
Resumen:
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/-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 -catenin at the cellular membrane, inhibition of the Wnt signalling and increase of apoptosis. We further demonstrate the involvement of LRP5 and the Wnt/-catenin signalling in the process because cellular differentiation can be rescued by the addition of downstream Wnt target genes to the monocytic cells.
Filiaciones:
Borrell-Pages, M:
Hosp Santa Creu & Sant Pau, IIB St Pau, CSIC ICCC, Cardiovasc Res Ctr, Barcelona, Spain
Romero, JC:
Hosp Santa Creu & Sant Pau, IIB St Pau, CSIC ICCC, Cardiovasc Res Ctr, Barcelona, Spain
Badimon, L:
Hosp Santa Creu & Sant Pau, IIB St Pau, CSIC ICCC, Cardiovasc Res Ctr, Barcelona, Spain
Inst Salud Carlos III, CIBEROBN, Barcelona, Spain
UAB, Cardiovasc Res Chair, Barcelona, Spain
Gold, Green Published
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