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Beta-catenin and transforming growth factor beta have distinct roles regulating fibroblast cell motility and the induction of collagen lattice contraction.

Poon R, Nik SA, Ahn J, Slade L, Alman BA - BMC Cell Biol. (2009)

Bottom Line: Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results.Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Raymond.poon@sickkids.ca

ABSTRACT

Background: beta-catenin and transforming growth factor beta signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor beta is partially mediated by beta-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of beta-catenin and its interaction with transforming growth factor beta in cell motility and the induction of collagen lattice contraction.

Results: Floating three dimensional collagen lattices seeded with cells expressing conditional and stabilized beta-catenin alleles, showed a modest negative relationship between beta-catenin level and the degree of lattice contraction. Transforming growth factor beta had a more dramatic effect, positively regulating lattice contraction. In contrast to the situation in the regulation of cell proliferation, this effect of transforming growth factor beta was not mediated by beta-catenin. Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results. Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.

Conclusion: This data demonstrates the complexity of the interaction of various signaling pathways in the regulation of cell behavior during wound repair. Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms. There is unlikely to be a single signaling pathway that acts as master regulator of fibroblast behavior in wound repair. beta-catenin plays dominant role regulating cell motility, while transforming growth factor beta plays a dominant role regulating the induction of collagen lattice contraction.

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Human fibroblasts induce collagen lattice contraction in a similar manner as murine firoblasts. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days are given for primary cultures from human fibroblasts treated with lithium, Dkk-1, TGF-β, or a carrier. There is a statistically significant difference for TGF-β treatment compared to carrier after day three. For lithium treatment there is a statistically significant difference for the time points with an asterisk above the data points. B. Representative photographs of the collagen lattices at day five.
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Figure 5: Human fibroblasts induce collagen lattice contraction in a similar manner as murine firoblasts. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days are given for primary cultures from human fibroblasts treated with lithium, Dkk-1, TGF-β, or a carrier. There is a statistically significant difference for TGF-β treatment compared to carrier after day three. For lithium treatment there is a statistically significant difference for the time points with an asterisk above the data points. B. Representative photographs of the collagen lattices at day five.

Mentions: To determine if human cells behaved the same as cells from mice, we examined human primary fibroblasts in a similar manner. Contraction was compared between cells treated with transforming growth factor β, Dkk-1, lithium, these agents in combination, or with controls. A similar pattern as found in the mouse cultures was observed. Lithium and Dkk-1 have a mild effect on lattice contraction, while transforming growth factor β has a more dramatic positive effect (Fig. 5). Dkk-1 and lithium had similar effects as in murine cultures, showing a mild negative effect of β-catenin on lattice contraction.


Beta-catenin and transforming growth factor beta have distinct roles regulating fibroblast cell motility and the induction of collagen lattice contraction.

Poon R, Nik SA, Ahn J, Slade L, Alman BA - BMC Cell Biol. (2009)

Human fibroblasts induce collagen lattice contraction in a similar manner as murine firoblasts. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days are given for primary cultures from human fibroblasts treated with lithium, Dkk-1, TGF-β, or a carrier. There is a statistically significant difference for TGF-β treatment compared to carrier after day three. For lithium treatment there is a statistically significant difference for the time points with an asterisk above the data points. B. Representative photographs of the collagen lattices at day five.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2691404&req=5

Figure 5: Human fibroblasts induce collagen lattice contraction in a similar manner as murine firoblasts. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days are given for primary cultures from human fibroblasts treated with lithium, Dkk-1, TGF-β, or a carrier. There is a statistically significant difference for TGF-β treatment compared to carrier after day three. For lithium treatment there is a statistically significant difference for the time points with an asterisk above the data points. B. Representative photographs of the collagen lattices at day five.
Mentions: To determine if human cells behaved the same as cells from mice, we examined human primary fibroblasts in a similar manner. Contraction was compared between cells treated with transforming growth factor β, Dkk-1, lithium, these agents in combination, or with controls. A similar pattern as found in the mouse cultures was observed. Lithium and Dkk-1 have a mild effect on lattice contraction, while transforming growth factor β has a more dramatic positive effect (Fig. 5). Dkk-1 and lithium had similar effects as in murine cultures, showing a mild negative effect of β-catenin on lattice contraction.

Bottom Line: Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results.Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Raymond.poon@sickkids.ca

ABSTRACT

Background: beta-catenin and transforming growth factor beta signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor beta is partially mediated by beta-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of beta-catenin and its interaction with transforming growth factor beta in cell motility and the induction of collagen lattice contraction.

Results: Floating three dimensional collagen lattices seeded with cells expressing conditional and stabilized beta-catenin alleles, showed a modest negative relationship between beta-catenin level and the degree of lattice contraction. Transforming growth factor beta had a more dramatic effect, positively regulating lattice contraction. In contrast to the situation in the regulation of cell proliferation, this effect of transforming growth factor beta was not mediated by beta-catenin. Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results. Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.

Conclusion: This data demonstrates the complexity of the interaction of various signaling pathways in the regulation of cell behavior during wound repair. Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms. There is unlikely to be a single signaling pathway that acts as master regulator of fibroblast behavior in wound repair. beta-catenin plays dominant role regulating cell motility, while transforming growth factor beta plays a dominant role regulating the induction of collagen lattice contraction.

Show MeSH
Related in: MedlinePlus