Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Logo for

J. Cell Biol. 152 (6): 1197-1206

Copyright © 2001 by the Rockefeller University Press.

© The Rockefeller University Press, /2001/3/1197/ $5.00
The Journal of Cell Biology, Volume 152, Number 6, March 19, 2001 1197-1206
Original Article The High Mobility Group (HMG) Boxes of the Nuclear Protein HMG1 Induce Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells Bernard Degrysea, Tiziana Bonaldib, Paola Scaffidib, Susanne Müllerb, Massimo Resnatib, Francesca Sanvitob, Gianluigi Arrigonib, and Marco E. Bianchib a Department of Genetics and Microbiology, University of Milan, 20133 Milan, Italy b Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milan, Italy Bernard Degryse, Department of Vascular Biology/VB-3, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Tel:(858) 784-7153 Fax:(858) 784-7353 E-mail:degryse{at}scripps.edu.

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.

atherosclerosis, chemotaxis, high mobility group 1, receptor of advanced glycation endproducts, smooth muscle cells

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
DEK Is a Poly(ADP-Ribose) Acceptor in Apoptosis and Mediates Resistance to Genotoxic Stress.
F. Kappes, J. Fahrer, M. S. Khodadoust, A. Tabbert, C. Strasser, N. Mor-Vaknin, M. Moreno-Villanueva, A. Burkle, D. M. Markovitz, and E. Ferrando-May (2008)
Mol. Cell. Biol. 28, 3245-3257
   Abstract »    Full Text »    PDF »
Parafibromin, a Component of the Human PAF Complex, Regulates Growth Factors and Is Required for Embryonic Development and Survival in Adult Mice.
P. Wang, M. R. Bowl, S. Bender, J. Peng, L. Farber, J. Chen, A. Ali, Z. Zhang, A. S. Alberts, R. V. Thakker, et al. (2008)
Mol. Cell. Biol. 28, 2930-2940
   Abstract »    Full Text »    PDF »
HMGB1 preconditioning: therapeutic application for a danger signal?.
J. R. Klune, T. R. Billiar, and A. Tsung (2008)
J. Leukoc. Biol. 83, 558-563
   Abstract »    Full Text »    PDF »
Sensing danger--Hsp72 and HMGB1 as candidate signals.
J. H. H. Williams and H. E. Ireland (2008)
J. Leukoc. Biol. 83, 489-492
   Abstract »    Full Text »    PDF »
The microtubule-targeting agent CA4P regresses leukemic xenografts by disrupting interaction with vascular cells and mitochondrial-dependent cell death.
I. Petit, M. A. Karajannis, L. Vincent, L. Young, J. Butler, A. T. Hooper, K. Shido, H. Steller, D. J. Chaplin, E. Feldman, et al. (2008)
Blood 111, 1951-1961
   Abstract »    Full Text »    PDF »
The Role of Nitric Oxide and the Unfolded Protein Response in Cytokine-Induced -Cell Death.
K. T. Chambers, J. A. Unverferth, S. M. Weber, R. C. Wek, F. Urano, and J. A. Corbett (2008)
Diabetes 57, 124-132
   Abstract »    Full Text »    PDF »
HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling.
A. Tsung, J. R. Klune, X. Zhang, G. Jeyabalan, Z. Cao, X. Peng, D. B. Stolz, D. A. Geller, M. R. Rosengart, and T. R. Billiar (2007)
J. Exp. Med. 204, 2913-2923
   Abstract »    Full Text »    PDF »
Multiple Effects of High Mobility Group Box Protein 1 in Skeletal Muscle Regeneration.
R. De Mori, S. Straino, A. Di Carlo, A. Mangoni, G. Pompilio, R. Palumbo, M. E. Bianchi, M. C. Capogrossi, and A. Germani (2007)
Arterioscler. Thromb. Vasc. Biol. 27, 2377-2383
   Abstract »    Full Text »    PDF »
Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-{kappa}B activation.
R. Palumbo, B. G. Galvez, T. Pusterla, F. De Marchis, G. Cossu, K. B. Marcu, and M. E. Bianchi (2007)
J. Cell Biol. 179, 33-40
   Abstract »    Full Text »    PDF »
Stage-Specific Secretion of HMGB1 in Cartilage Regulates Endochondral Ossification.
N. Taniguchi, K. Yoshida, T. Ito, M. Tsuda, Y. Mishima, T. Furumatsu, L. Ronfani, K. Abeyama, K.-i. Kawahara, S. Komiya, et al. (2007)
Mol. Cell. Biol. 27, 5650-5663
   Abstract »    Full Text »    PDF »
The Anti-inflammatory Effects of Heat Shock Protein 72 Involve Inhibition of High-Mobility-Group Box 1 Release and Proinflammatory Function in Macrophages.
D. Tang, R. Kang, W. Xiao, H. Wang, S. K. Calderwood, and X. Xiao (2007)
J. Immunol. 179, 1236-1244
   Abstract »    Full Text »    PDF »
Post-translational Methylation of High Mobility Group Box 1 (HMGB1) Causes Its Cytoplasmic Localization in Neutrophils.
I. Ito, J. Fukazawa, and M. Yoshida (2007)
J. Biol. Chem. 282, 16336-16344
   Abstract »    Full Text »    PDF »
Nuclear Heat Shock Protein 72 as a Negative Regulator of Oxidative Stress (Hydrogen Peroxide)-Induced HMGB1 Cytoplasmic Translocation and Release.
D. Tang, R. Kang, W. Xiao, L. Jiang, M. Liu, Y. Shi, K. Wang, H. Wang, and X. Xiao (2007)
J. Immunol. 178, 7376-7384
   Abstract »    Full Text »    PDF »
Masquerader: High Mobility Group Box-1 and Cancer.
J. E. Ellerman, C. K. Brown, M. de Vera, H. J. Zeh, T. Billiar, A. Rubartelli, and M. T. Lotze (2007)
Clin. Cancer Res. 13, 2836-2848
   Abstract »    Full Text »    PDF »
High-Mobility Group Box 1 Activates Integrin-Dependent Homing of Endothelial Progenitor Cells.
E. Chavakis, A. Hain, M. Vinci, G. Carmona, M. E. Bianchi, P. Vajkoczy, A. M. Zeiher, T. Chavakis, and S. Dimmeler (2007)
Circ. Res. 100, 204-212
   Abstract »    Full Text »    PDF »
DAMPs, PAMPs and alarmins: all we need to know about danger.
M. E. Bianchi (2007)
J. Leukoc. Biol. 81, 1-5
   Abstract »    Full Text »    PDF »
High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin.
D. Yang, Q. Chen, H. Yang, K. J. Tracey, M. Bustin, and J. J. Oppenheim (2007)
J. Leukoc. Biol. 81, 59-66
   Abstract »    Full Text »    PDF »
Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice.
G. Sitia, M. Iannacone, S. Muller, M. E. Bianchi, and L. G. Guidotti (2007)
J. Leukoc. Biol. 81, 100-107
   Abstract »    Full Text »    PDF »
HMGB1-secreting capacity of multiple cell lineages revealed by a novel HMGB1 ELISPOT assay.
H. Wahamaa, T. Vallerskog, S. Qin, C. Lunderius, G. LaRosa, U. Andersson, and H. E. Harris (2007)
J. Leukoc. Biol. 81, 129-136
   Abstract »    Full Text »    PDF »
Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury.
A. Tsung, N. Zheng, G. Jeyabalan, K. Izuishi, J. R. Klune, D. A. Geller, M. T. Lotze, L. Lu, and T. R. Billiar (2007)
J. Leukoc. Biol. 81, 119-128
   Abstract »    Full Text »    PDF »
Nucleocytoplasmic Shuttling of HMGB1 Is Regulated by Phosphorylation That Redirects It toward Secretion.
J. H. Youn and J.-S. Shin (2006)
J. Immunol. 177, 7889-7897
   Abstract »    Full Text »    PDF »
Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1 protein.
A. Porto, R. Palumbo, M. Pieroni, G. Aprigliano, R. Chiesa, F. Sanvito, A. Maseri, and M. E. Bianchi (2006)
FASEB J 20, 2565-2566
   Abstract »    Full Text »    PDF »
The high mobility group box chromosomal protein 1 is expressed in the human and rat testis where it may function as an antibacterial factor.
C. K. Zetterstrom, M.-L. Strand, and O. Soder (2006)
Hum. Reprod. 21, 2801-2809
   Abstract »    Full Text »    PDF »
Contribution of High-Mobility Group Box-1 to the Development of Ventilator-induced Lung Injury.
E. N. Ogawa, A. Ishizaka, S. Tasaka, H. Koh, H. Ueno, F. Amaya, M. Ebina, S. Yamada, Y. Funakoshi, J. Soejima, et al. (2006)
Am. J. Respir. Crit. Care Med. 174, 400-407
   Abstract »    Full Text »    PDF »
Activation of sPLA2-IIA and PGE2 production by high mobility group protein B1 in vascular smooth muscle cells sensitized by IL-1{beta}.
A. Jaulmes, S. Thierry, B. Janvier, M. Raymondjean, and V. Marechal (2006)
FASEB J 20, 1727-1729
   Abstract »    Full Text »    PDF »
Cutting Edge: High-Mobility Group Box 1 Preconditioning Protects against Liver Ischemia-Reperfusion Injury..
K. Izuishi, A. Tsung, G. Jeyabalan, N. D. Critchlow, J. Li, K. J. Tracey, R. A. Demarco, M. T. Lotze, M. P. Fink, D. A. Geller, et al. (2006)
J. Immunol. 176, 7154-7158
   Abstract »    Full Text »    PDF »
High mobility group box 1 protein interacts with multiple Toll-like receptors.
J. S. Park, F. Gamboni-Robertson, Q. He, D. Svetkauskaite, J.-Y. Kim, D. Strassheim, J.-W. Sohn, S. Yamada, I. Maruyama, A. Banerjee, et al. (2006)
Am J Physiol Cell Physiol 290, C917-C924
   Abstract »    Full Text »    PDF »
Cutting Edge: Extracellular High Mobility Group Box-1 Protein Is a Proangiogenic Cytokine.
S. Mitola, M. Belleri, C. Urbinati, D. Coltrini, B. Sparatore, M. Pedrazzi, E. Melloni, and M. Presta (2006)
J. Immunol. 176, 12-15
   Abstract »    Full Text »    PDF »
Exogenous High-Mobility Group Box 1 Protein Induces Myocardial Regeneration After Infarction via Enhanced Cardiac C-Kit+ Cell Proliferation and Differentiation.
F. Limana, A. Germani, A. Zacheo, J. Kajstura, A. Di Carlo, G. Borsellino, O. Leoni, R. Palumbo, L. Battistini, R. Rastaldo, et al. (2005)
Circ. Res. 97, e73-e83
   Abstract »    Full Text »    PDF »
Differential Proteomic Analysis of Bronchoalveolar Lavage Fluid in Asthmatics following Segmental Antigen Challenge.
J. Wu, M. Kobayashi, E. A. Sousa, W. Liu, J. Cai, S. J. Goldman, A. J. Dorner, S. J. Projan, M. S. Kavuru, Y. Qiu, et al. (2005)
Mol. Cell. Proteomics 4, 1251-1264
   Abstract »    Full Text »    PDF »
The cytokine activity of HMGB1.
H. Yang, H. Wang, C. J. Czura, and K. J. Tracey (2005)
J. Leukoc. Biol. 78, 1-8
   Abstract »    Full Text »    PDF »
Specific Interference of Urokinase-type Plasminogen Activator Receptor and Matrix Metalloproteinase-9 Gene Expression Induced by Double-stranded RNA Results in Decreased Invasion, Tumor Growth, and Angiogenesis in Gliomas.
S. S. Lakka, C. S. Gondi, D. H. Dinh, W. C. Olivero, M. Gujrati, V. H. Rao, C. Sioka, and J. S. Rao (2005)
J. Biol. Chem. 280, 21882-21892
   Abstract »    Full Text »    PDF »
The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion.
A. Tsung, R. Sahai, H. Tanaka, A. Nakao, M. P. Fink, M. T. Lotze, H. Yang, J. Li, K. J. Tracey, D. A. Geller, et al. (2005)
J. Exp. Med. 201, 1135-1143
   Abstract »    Full Text »    PDF »
Angiogenetic Signaling through Hypoxia: HMGB1: An Angiogenetic Switch Molecule.
C. Schlueter, H. Weber, B. Meyer, P. Rogalla, K. Roser, S. Hauke, and J. Bullerdiek (2005)
Am. J. Pathol. 166, 1259-1263
   Abstract »    Full Text »    PDF »
Colon Cancer Cell-Derived High Mobility Group 1/Amphoterin Induces Growth Inhibition and Apoptosis in Macrophages.
H. Kuniyasu, S. Yano, T. Sasaki, T. Sasahira, S. Sone, and H. Ohmori (2005)
Am. J. Pathol. 166, 751-760
   Abstract »    Full Text »    PDF »
Contributions of High Mobility Group Box Protein in Experimental and Clinical Acute Lung Injury.
H. Ueno, T. Matsuda, S. Hashimoto, F. Amaya, Y. Kitamura, M. Tanaka, A. Kobayashi, I. Maruyama, S. Yamada, N. Hasegawa, et al. (2004)
Am. J. Respir. Crit. Care Med. 170, 1310-1316
   Abstract »    Full Text »    PDF »
Increased Expression of the DNA-Binding Cytokine HMGB1 in Human Atherosclerotic Lesions: Role of Activated Macrophages and Cytokines.
N. Kalinina, A. Agrotis, Y. Antropova, G. DiVitto, P. Kanellakis, G. Kostolias, O. Ilyinskaya, E. Tararak, and A. Bobik (2004)
Arterioscler. Thromb. Vasc. Biol. 24, 2320-2325
   Abstract »    Full Text »    PDF »
Regulation of monocyte migration by amphoterin (HMGB1).
A. Rouhiainen, J. Kuja-Panula, E. Wilkman, J. Pakkanen, J. Stenfors, R. K. Tuominen, M. Lepantalo, O. Carpen, J. Parkkinen, and H. Rauvala (2004)
Blood 104, 1174-1182
   Abstract »    Full Text »    PDF »
The Low Density Lipoprotein Receptor-related Protein Is a Motogenic Receptor for Plasminogen Activator Inhibitor-1.
B. Degryse, J. G. Neels, R.-P. Czekay, K. Aertgeerts, Y.-i. Kamikubo, and D. J. Loskutoff (2004)
J. Biol. Chem. 279, 22595-22604
   Abstract »    Full Text »    PDF »
Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation.
R. Palumbo, M. Sampaolesi, F. De Marchis, R. Tonlorenzi, S. Colombetti, A. Mondino, G. Cossu, and M. E. Bianchi (2004)
J. Cell Biol. 164, 441-449
   Abstract »    Full Text »    PDF »
The mechanism of cell death during West Nile virus infection is dependent on initial infectious dose.
J. J. H. Chu and M. L. Ng (2003)
J. Gen. Virol. 84, 3305-3314
   Abstract »    Full Text »    PDF »
Activation of gene expression in human neutrophils by high mobility group box 1 protein.
J. S. Park, J. Arcaroli, H.-K. Yum, H. Yang, H. Wang, K.-Y. Yang, K.-H. Choe, D. Strassheim, T. M. Pitts, K. J. Tracey, et al. (2003)
Am J Physiol Cell Physiol 284, C870-C879
   Abstract »    Full Text »    PDF »
IFN-{gamma} Induces High Mobility Group Box 1 Protein Release Partly Through a TNF-Dependent Mechanism.
B. Rendon-Mitchell, M. Ochani, J. Li, J. Han, H. Wang, H. Yang, S. Susarla, C. Czura, R. A. Mitchell, G. Chen, et al. (2003)
J. Immunol. 170, 3890-3897
   Abstract »    Full Text »    PDF »
Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells.
C. Fiuza, M. Bustin, S. Talwar, M. Tropea, E. Gerstenberger, J. H. Shelhamer, and A. F. Suffredini (2003)
Blood 101, 2652-2660
   Abstract »    Full Text »    PDF »
HMGB1 as a cytokine and therapeutic target.
Huan Yang, Haichao Wang, C. J. Czura, and K. J. Tracey (2002)
Innate Immunity 8, 469-472
   Abstract »    PDF »
HMGB1 as a DNA-binding cytokine.
U. Andersson, H. Erlandsson-Harris, H. Yang, and K. J. Tracey (2002)
J. Leukoc. Biol. 72, 1084-1091
   Abstract »    Full Text »    PDF »
HMGB1 Interacts with Many Apparently Unrelated Proteins by Recognizing Short Amino Acid Sequences.
A. Dintilhac and J. Bernues (2002)
J. Biol. Chem. 277, 7021-7028
   Abstract »    Full Text »    PDF »
HMGB1 as a Late Mediator of Lethal Systemic Inflammation.
H. WANG, H. YANG, C. J. CZURA, A. E. SAMA, and K. J. TRACEY (2001)
Am. J. Respir. Crit. Care Med. 164, 1768-1773
   Full Text »    PDF »
Prostaglandin H Synthase and Vascular Function.
S. T. Davidge (2001)
Circ. Res. 89, 650-660
   Abstract »    Full Text »    PDF »

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)