Functional blockade of á5â1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells.

VELLóN L.; ROYO F.; MATTHIESEN R.; TORRES-FUENZALIDA J.; LORENTI A.; PARADA L.A.

BMC CELL BIOLOGY

BIOMED CENTRAL LTD

Año: 2010 vol. 11 p. 81 - 89

1471-2121

BACKGROUND: Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of á5â1 integrin in liver progenitor cells. RESULTS: Cells treated with a specific antibody against á5â1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus. CONCLUSION: Collectively, our results demonstrate that á5â1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.