Published online before print April 24, 2003, doi: 10.1161/01.RES.0000074000.03562.CC
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 18, 2002
Revised on April 16, 2003
Accepted on April 16, 2003
AIF-1 Is an Actin-Polymerizing and Rac1-Activating Protein That Promotes Vascular Smooth Muscle Cell Migration
Michael V. Autieri *;
From the Departments of Physiology (M.V.A.) and Cardiology (S.E.K., K.W.W.), Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pa.
* To whom correspondence should be addressed. E-mail: mautieri{at}unix.temple.edu.
Development of vascular restenosis is a multifaceted process characterized by migration and proliferation of vascular smooth muscle cells (VSMCs), resulting in loss of lumen diameter. Characterization of proteins that mediate this process is essential in our understanding of the pathogenesis of arterial injury. Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, calcium-binding protein that is expressed in VSMCs by allograft and balloon angioplasty injury. AIF-1 is not present in cultured human VSMCs but is induced by cytokines, and overexpression of AIF-1 results in increased VSMC growth and cell-cycle gene expression. To characterize AIF-1 modulatory effects in primary human VSMCs, AIF-1-interacting proteins were identified by an AIF-1/glutathione S transferase fusion protein affinity assay. MALDI-TOF mass spectrophotometric amino analysis identified actin as an AIF-1 interacting protein. This interaction was verified by coimmunoprecipitation. This is a functional interaction, because AIF-1 binds to and polymerizes F-actin in vitro. In unstimulated VSMCs, AIF-1 colocalizes with F-actin but translocates to lamellipodia on stimulation with platelet-derived growth factor. VSMCs stably transduced with AIF-1 retrovirus migrate 2.6-fold more rapidly (85.1±2.9 versus 225.5±16.6; P<0.001) in response to platelet-derived growth factor versus control cells. AIF-1 colocalizes with Rac1, and AIF-1-transduced VSMCs show a constitutive and enhanced activation of Rac1, providing a mechanism for the increased migration. These data indicate that AIF-1 binds and polymerizes F actin and also regulates Rac1 activity and VSMC migration. Considering the AIF-1 expression pattern in injured arteries, this suggests that AIF-1 may be involved in the cytoskeletal signaling network leading to vascular remodeling.
Key words: allograft inflammatory factor-1 • smooth muscle cell • migration • Rac1
This article has been cited by other articles:
 |
|
 |
|
  L. J. Sommerville, C. Xing, S. E. Kelemen, S. Eguchi, and M. V. Autieri Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity Cardiovasc Res, October 1, 2008; (2008) cvn242v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Sommerville, S. E. Kelemen, and M. V. Autieri Increased Smooth Muscle Cell Activation and Neointima Formation in Response to Injury in AIF-1 Transgenic Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 47 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Litvin, X. Chen, S. Keleman, S. Zhu, and M. Autieri Expression and function of periostin-like factor in vascular smooth muscle cells Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1672 - C1680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tian and M. V. Autieri Cytokine expression and AIF-1-mediated activation of Rac2 in vascular smooth muscle cells: a role for Rac2 in VSMC activation Am J Physiol Cell Physiol, February 1, 2007; 292(2): C841 - C849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. K. Tan, X. Zhou, M. D. Mayes, P. Gourh, X. Guo, C. Marcum, L. Jin, and F. C. Arnett Jr Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients Rheumatology, June 1, 2006; 45(6): 694 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tian, S. E. Kelemen, and M. V. Autieri Inhibition of AIF-1 expression by constitutive siRNA expression reduces macrophage migration, proliferation, and signal transduction initiated by atherogenic stimuli Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1083 - C1091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. F. Yang, D. W. Ho, C. K. Lau, C. T. Lam, C. T. Lum, R. T. P. Poon, and S. T. Fan Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages Int. Immunol., November 1, 2005; 17(11): 1391 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Kelemen and M. V. Autieri Expression of Allograft Inflammatory Factor-1 in T Lymphocytes: A Role in T-Lymphocyte Activation and Proliferative Arteriopathies Am. J. Pathol., August 1, 2005; 167(2): 619 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Nair, H. Del Valle, P. S. Gross, D. P. Terwilliger, and L. C. Smith Macroarray analysis of coelomocyte gene expression in response to LPS in the sea urchin. Identification of unexpected immune diversity in an invertebrate Physiol Genomics, June 16, 2005; 22(1): 33 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, S. E. Kelemen, and M. V. Autieri Expression of granulocyte colony-stimulating factor is induced in injured rat carotid arteries and mediates vascular smooth muscle cell migration Am J Physiol Cell Physiol, January 1, 2005; 288(1): C81 - C88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, S. E. Kelemen, and M. V. Autieri AIF-1 Expression Modulates Proliferation of Human Vascular Smooth Muscle Cells by Autocrine Expression of G-CSF Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1217 - 1222. [Abstract] [Full Text] [PDF]
|
|