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 Gi/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.
| Original language | English |
|---|---|
| Pages (from-to) | 1197-1206 |
| Number of pages | 10 |
| Journal | Journal of Cell Biology |
| Volume | 152 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 19 2001 |
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Keywords
- Atherosclerosis
- Chemotaxis
- High mobility group 1
- Receptor of advanced glycation endproducts
- Smooth muscle cells
ASJC Scopus subject areas
- Cell Biology
Cite this
The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. / Degryse, Bernard; Bonaldi, Tiziana; Scaffidi, Paola; Müller, Susanne; Resnati, Massimo; Sanvito, Francesca; Arrigoni, Gianluigi; Bianchi, Marco E.
In: Journal of Cell Biology, Vol. 152, No. 6, 19.03.2001, p. 1197-1206.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells
AU - Degryse, Bernard
AU - Bonaldi, Tiziana
AU - Scaffidi, Paola
AU - Müller, Susanne
AU - Resnati, Massimo
AU - Sanvito, Francesca
AU - Arrigoni, Gianluigi
AU - Bianchi, Marco E.
PY - 2001/3/19
Y1 - 2001/3/19
N2 - 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 Gi/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.
AB - 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 Gi/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.
KW - Atherosclerosis
KW - Chemotaxis
KW - High mobility group 1
KW - Receptor of advanced glycation endproducts
KW - Smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=0035911959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035911959&partnerID=8YFLogxK
U2 - 10.1083/jcb.152.6.1197
DO - 10.1083/jcb.152.6.1197
M3 - Article
C2 - 11257120
AN - SCOPUS:0035911959
VL - 152
SP - 1197
EP - 1206
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -