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The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells.

Degryse B, Bonaldi T, Scaffidi P, Müller S, Resnati M, Sanvito F, Arrigoni G, Bianchi ME - J. Cell Biol. (2001)

Bottom Line: HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays.HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells.These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Microbiology, University of Milan, 20133 Milan, Italy. degryse@scripps.edu

ABSTRACT
HMG1 (high mobility group 1) is a ubiquitous and abundant chromatin component. However, HMG1 can be secreted by activated macrophages and monocytes, and can act as a mediator of inflammation and endotoxic lethality. Here we document a role of extracellular HMG1 in cell migration. HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays. HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells. These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses. Pertussis toxin and the mitogen-activated protein kinase kinase inhibitor PD98059 also blocked HMG1-induced rat smooth muscle cell migration, suggesting that a G(i/o) protein and mitogen-activated protein kinases are required for the HMG1 signaling pathway. We also show that HMG1 can be released by damage or necrosis of a variety of cell types, including endothelial cells. Thus, HMG1 has all the hallmarks of a molecule that can promote atherosclerosis and restenosis after vascular damage.

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Related in: MedlinePlus

Chemotactic response of RSMC to the HMG box domains of HMG1. (A) Concentration-dependent response to Box A and Box B, both expressed in E. coli. Random cell migration is referred to as 100% migration. The data represent the mean ± SD (n = 3). The statistical significance of the result is P < 0.0001 in an ANOVA model, for both Box A and Box B. (B) Effects of full-length HMG1 expressed in E. coli (100 ng/ml), Box A+B (100 ng/ml), Box A (10 ng/ml), or Box B (10 ng/ml) on actin cytoskeleton organization. Cells were incubated with the indicated molecule for 30 min. Actin filaments were visualized using TRITC-phalloidin.
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Figure 3: Chemotactic response of RSMC to the HMG box domains of HMG1. (A) Concentration-dependent response to Box A and Box B, both expressed in E. coli. Random cell migration is referred to as 100% migration. The data represent the mean ± SD (n = 3). The statistical significance of the result is P < 0.0001 in an ANOVA model, for both Box A and Box B. (B) Effects of full-length HMG1 expressed in E. coli (100 ng/ml), Box A+B (100 ng/ml), Box A (10 ng/ml), or Box B (10 ng/ml) on actin cytoskeleton organization. Cells were incubated with the indicated molecule for 30 min. Actin filaments were visualized using TRITC-phalloidin.

Mentions: Full-length HMG1 from E. coli induced a dose-dependent chemotactic effect on RSMC with a maximum, about twofold above control, at 100 ng/ml. Box A+B (not shown), Box A, and Box B also stimulated RSMC migration in a concentration-dependent manner. However, these maxima were not obtained within the same range of concentrations: the effect of Box A was maximal at 1–10 ng/ml, whereas the chemotactic effect of Box B peaked at 10–100 ng/ml (Fig. 3 A).


The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells.

Degryse B, Bonaldi T, Scaffidi P, Müller S, Resnati M, Sanvito F, Arrigoni G, Bianchi ME - J. Cell Biol. (2001)

Chemotactic response of RSMC to the HMG box domains of HMG1. (A) Concentration-dependent response to Box A and Box B, both expressed in E. coli. Random cell migration is referred to as 100% migration. The data represent the mean ± SD (n = 3). The statistical significance of the result is P < 0.0001 in an ANOVA model, for both Box A and Box B. (B) Effects of full-length HMG1 expressed in E. coli (100 ng/ml), Box A+B (100 ng/ml), Box A (10 ng/ml), or Box B (10 ng/ml) on actin cytoskeleton organization. Cells were incubated with the indicated molecule for 30 min. Actin filaments were visualized using TRITC-phalloidin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199202&req=5

Figure 3: Chemotactic response of RSMC to the HMG box domains of HMG1. (A) Concentration-dependent response to Box A and Box B, both expressed in E. coli. Random cell migration is referred to as 100% migration. The data represent the mean ± SD (n = 3). The statistical significance of the result is P < 0.0001 in an ANOVA model, for both Box A and Box B. (B) Effects of full-length HMG1 expressed in E. coli (100 ng/ml), Box A+B (100 ng/ml), Box A (10 ng/ml), or Box B (10 ng/ml) on actin cytoskeleton organization. Cells were incubated with the indicated molecule for 30 min. Actin filaments were visualized using TRITC-phalloidin.
Mentions: Full-length HMG1 from E. coli induced a dose-dependent chemotactic effect on RSMC with a maximum, about twofold above control, at 100 ng/ml. Box A+B (not shown), Box A, and Box B also stimulated RSMC migration in a concentration-dependent manner. However, these maxima were not obtained within the same range of concentrations: the effect of Box A was maximal at 1–10 ng/ml, whereas the chemotactic effect of Box B peaked at 10–100 ng/ml (Fig. 3 A).

Bottom Line: HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays.HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells.These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Microbiology, University of Milan, 20133 Milan, Italy. degryse@scripps.edu

ABSTRACT
HMG1 (high mobility group 1) is a ubiquitous and abundant chromatin component. However, HMG1 can be secreted by activated macrophages and monocytes, and can act as a mediator of inflammation and endotoxic lethality. Here we document a role of extracellular HMG1 in cell migration. HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays. HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells. These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses. Pertussis toxin and the mitogen-activated protein kinase kinase inhibitor PD98059 also blocked HMG1-induced rat smooth muscle cell migration, suggesting that a G(i/o) protein and mitogen-activated protein kinases are required for the HMG1 signaling pathway. We also show that HMG1 can be released by damage or necrosis of a variety of cell types, including endothelial cells. Thus, HMG1 has all the hallmarks of a molecule that can promote atherosclerosis and restenosis after vascular damage.

Show MeSH
Related in: MedlinePlus