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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

HMG1 is present in the nuclei of endothelial cells, but not in those of vascular SMC. (A and B). HMG1 is present in the nuclei of endothelial cells, but is not detectable in the nuclei of vascular SMC. Shown is a section of a human pancreatic artery, stained with anti–HMG1 antibody and counterstained with hematoxylin, at low (A) and high (B) magnification. The red frame indicates the location of the area shown in B, and the arrows point to the nuclei of SMC. (C) Western blot analysis showing the expression level of HMG1 in RSMC in comparison to HeLa cells. The indicated number of cells were lysed directly in SDS-PAGE sample buffer and loaded onto the gel. After the detection of HMG1 (which is identical in rat and human), the blot was stripped and subsequently stained with antihistone antibodies to check for loading.
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Figure 9: HMG1 is present in the nuclei of endothelial cells, but not in those of vascular SMC. (A and B). HMG1 is present in the nuclei of endothelial cells, but is not detectable in the nuclei of vascular SMC. Shown is a section of a human pancreatic artery, stained with anti–HMG1 antibody and counterstained with hematoxylin, at low (A) and high (B) magnification. The red frame indicates the location of the area shown in B, and the arrows point to the nuclei of SMC. (C) Western blot analysis showing the expression level of HMG1 in RSMC in comparison to HeLa cells. The indicated number of cells were lysed directly in SDS-PAGE sample buffer and loaded onto the gel. After the detection of HMG1 (which is identical in rat and human), the blot was stripped and subsequently stained with antihistone antibodies to check for loading.

Mentions: Immunohistochemistry confirmed that HMG1 is contained in the nuclei of endothelial cells that line human arteries (Fig. 9). Surprisingly, we found that most nuclei of smooth muscle cells in the same arteries (Fig. 9 B, arrows) contain an undetectable amount of HMG1. RMSC in culture in vitro also contain a very small amount of HMG1 compared with HeLa cells (Fig. 9 C).


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)

HMG1 is present in the nuclei of endothelial cells, but not in those of vascular SMC. (A and B). HMG1 is present in the nuclei of endothelial cells, but is not detectable in the nuclei of vascular SMC. Shown is a section of a human pancreatic artery, stained with anti–HMG1 antibody and counterstained with hematoxylin, at low (A) and high (B) magnification. The red frame indicates the location of the area shown in B, and the arrows point to the nuclei of SMC. (C) Western blot analysis showing the expression level of HMG1 in RSMC in comparison to HeLa cells. The indicated number of cells were lysed directly in SDS-PAGE sample buffer and loaded onto the gel. After the detection of HMG1 (which is identical in rat and human), the blot was stripped and subsequently stained with antihistone antibodies to check for loading.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: HMG1 is present in the nuclei of endothelial cells, but not in those of vascular SMC. (A and B). HMG1 is present in the nuclei of endothelial cells, but is not detectable in the nuclei of vascular SMC. Shown is a section of a human pancreatic artery, stained with anti–HMG1 antibody and counterstained with hematoxylin, at low (A) and high (B) magnification. The red frame indicates the location of the area shown in B, and the arrows point to the nuclei of SMC. (C) Western blot analysis showing the expression level of HMG1 in RSMC in comparison to HeLa cells. The indicated number of cells were lysed directly in SDS-PAGE sample buffer and loaded onto the gel. After the detection of HMG1 (which is identical in rat and human), the blot was stripped and subsequently stained with antihistone antibodies to check for loading.
Mentions: Immunohistochemistry confirmed that HMG1 is contained in the nuclei of endothelial cells that line human arteries (Fig. 9). Surprisingly, we found that most nuclei of smooth muscle cells in the same arteries (Fig. 9 B, arrows) contain an undetectable amount of HMG1. RMSC in culture in vitro also contain a very small amount of HMG1 compared with HeLa cells (Fig. 9 C).

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