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Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells.

Vellón L, Royo F, Matthiesen R, Torres-Fuenzalida J, Lorenti A, Parada LA - BMC Cell Biol. (2010)

Bottom Line: Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration.These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cytogenomics, CIC bioGUNE-CIBEREHD, Par, Tec, Bizkaia Ed, 801 A, 48160 - Derio, Spain.

ABSTRACT

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 α5β1 integrin in liver progenitor cells.

Results: Cells treated with a specific antibody against α5β1 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 α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

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Changes in the expression level of genes encoding chromatin remodeling and transcription factors in MLP29 cells during migration. (A) Changes in the expression level of genes encoding chromatin remodeling factors were plotted according to their level of significance as a color-encoded map, in which a p-value close to 1 indicates significant up-regulation, and a p-value close to 0 indicates a significant down-regulation. (B) Changes in the expression level of transcription factors following the treatment with α5β1 integrin blocking antibody or with HGF/SF1 for 24 hours.
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Figure 5: Changes in the expression level of genes encoding chromatin remodeling and transcription factors in MLP29 cells during migration. (A) Changes in the expression level of genes encoding chromatin remodeling factors were plotted according to their level of significance as a color-encoded map, in which a p-value close to 1 indicates significant up-regulation, and a p-value close to 0 indicates a significant down-regulation. (B) Changes in the expression level of transcription factors following the treatment with α5β1 integrin blocking antibody or with HGF/SF1 for 24 hours.

Mentions: A total of 32 genes, belonging to the Smarc (SWI/SNF-related, matrix-associated, actin-dependent regulators of chromatin) family of chromatin remodeling factors were represented in the array and the analysis of their expression data revealed that functional blockade of α5β1 resulted in a larger number of differentially regulated genes than HGF/SF1 stimulation (Figure 5). We also analyzed the expression level of transcription factors, and our results demonstrate drastic changes in the expression level in integrin inhibited cells, whereas stimulation with HGF/SF1 presented a more restricted response (Figure 5). More importantly, the transcriptional responses to these two treatments are clearly distinct, indicating that the genomic effects exerted by the disruption of cell-ECM interactions differ from those induced by soluble regulatory factors (HGF/SF1), possibly because cells also apply traction to their integrin receptors, in addition to the integrin ligation-induced signaling.


Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells.

Vellón L, Royo F, Matthiesen R, Torres-Fuenzalida J, Lorenti A, Parada LA - BMC Cell Biol. (2010)

Changes in the expression level of genes encoding chromatin remodeling and transcription factors in MLP29 cells during migration. (A) Changes in the expression level of genes encoding chromatin remodeling factors were plotted according to their level of significance as a color-encoded map, in which a p-value close to 1 indicates significant up-regulation, and a p-value close to 0 indicates a significant down-regulation. (B) Changes in the expression level of transcription factors following the treatment with α5β1 integrin blocking antibody or with HGF/SF1 for 24 hours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967514&req=5

Figure 5: Changes in the expression level of genes encoding chromatin remodeling and transcription factors in MLP29 cells during migration. (A) Changes in the expression level of genes encoding chromatin remodeling factors were plotted according to their level of significance as a color-encoded map, in which a p-value close to 1 indicates significant up-regulation, and a p-value close to 0 indicates a significant down-regulation. (B) Changes in the expression level of transcription factors following the treatment with α5β1 integrin blocking antibody or with HGF/SF1 for 24 hours.
Mentions: A total of 32 genes, belonging to the Smarc (SWI/SNF-related, matrix-associated, actin-dependent regulators of chromatin) family of chromatin remodeling factors were represented in the array and the analysis of their expression data revealed that functional blockade of α5β1 resulted in a larger number of differentially regulated genes than HGF/SF1 stimulation (Figure 5). We also analyzed the expression level of transcription factors, and our results demonstrate drastic changes in the expression level in integrin inhibited cells, whereas stimulation with HGF/SF1 presented a more restricted response (Figure 5). More importantly, the transcriptional responses to these two treatments are clearly distinct, indicating that the genomic effects exerted by the disruption of cell-ECM interactions differ from those induced by soluble regulatory factors (HGF/SF1), possibly because cells also apply traction to their integrin receptors, in addition to the integrin ligation-induced signaling.

Bottom Line: Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration.These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cytogenomics, CIC bioGUNE-CIBEREHD, Par, Tec, Bizkaia Ed, 801 A, 48160 - Derio, Spain.

ABSTRACT

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 α5β1 integrin in liver progenitor cells.

Results: Cells treated with a specific antibody against α5β1 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 α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.

Show MeSH
Related in: MedlinePlus