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

Bernard Degryse, Tiziana Bonaldi, Paola Scaffidi, Susanne Müller, Massimo Resnati, Francesca Sanvito, Gianluigi Arrigoni, Marco E. Bianchi

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1197-1206
Number of pages10
JournalJournal of Cell Biology
Volume152
Issue number6
DOIs
Publication statusPublished - Mar 19 2001

Fingerprint

HMGB Proteins
Chemotaxis
Nuclear Proteins
Cytoskeleton
Smooth Muscle Myocytes
Cell Movement
Inflammation Mediators
Cell Shape
Mitogen-Activated Protein Kinase Kinases
Pertussis Toxin
Mitogen-Activated Protein Kinases
Actin Cytoskeleton
Wound Healing
Chromatin
Blood Vessels
Monocytes
Atherosclerosis
Necrosis
Endothelial Cells
Macrophages

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 journalArticle

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