Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway.
Smooth muscle cell (SMC) migration involves interactions of integrin receptors with extracellular matrix (ECM) and is an important process of neointimal formation in atherosclerosis and restenosis after vascular interventions. Previous studies have shown that periostin (PN), a novel ECM protein, is upregulated in rat carotid artery after balloon injury, and growth factor-stimulated expression of PN promotes SMC migration in vitro. Here, we address the mechanism by which PN-integrin interaction mediates SMC migration in vitro. Aortic SMCs isolated from PN null mice exhibited a significantly reduced ability to migrate and proliferate in vitro. Endogenous PN protein was absent and very low in the culture medium from the primary cultures of PN-/- and wildtype SMCs, respectively. In both types of SMCs, adenovirus-mediated overexpression of HA-tagged PN to a similar extent, which induced a robust cell migration concomitantly with an increase in beta3-integrin expression and phosphorylation of FAK (Tyr397). Furthermore, in cultured human SMCs, specific integrin blocking antibodies showed that interactions of PN-alphanubeta3 and PN-alphanubeta5, but not PN-beta1 integrins, are required for SMC migration. Inhibition of FAK signaling by overexpression of an endogenous FAK inhibitor termed FRNK (FAK-related nonkinase) significantly attenuated FAK (Tyr397) phosphorylation and the SMC migration induced by PN. These results reveal a mechanism whereby PN mediates vascular SMC migration through an interaction with alphaV-integrins (mainly alphanubeta3) and subsequent activation of FAK pathway.
Li
Guohong
G
Department of Neurosurgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, United States. gli@lsuhsc.edu
Jin
Rong
R
Norris
Russell A
RA
Zhang
Lin
L
Yu
Shiyong
S
Wu
Fusheng
F
Markwald
Roger R
RR
Nanda
Anil
A
Conway
Simon J
SJ
Smyth
Susan S
SS
Granger
D Neil
DN
D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D005434:Flow Cytometry / Q000379:methods; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; C512835:POSTN protein, human; C082838:Postn protein, mouse; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D051416:Focal Adhesion Protein-Tyrosine Kinases
Mol Cell Biol. 2004 May;24(9):3992-4003
15082792
J Exp Med. 2008 Feb 18;205(2):295-303
18208976
Cancer Res. 2002 Sep 15;62(18):5358-64
12235007
J Biol Chem. 2008 Oct 3;283(40):26839-49
18669633
Oncogene. 2007 Mar 29;26(14):2082-94
17043657
Cardiovasc Res. 2007 Sep 1;75(4):738-47
17574222
Biochem J. 1993 Aug 15;294 ( Pt 1):271-8
8363580
Science. 1991 Sep 6;253(5024):1129-32
1653454
J Cell Biochem. 2007 Jun 1;101(3):695-711
17226767
Exp Cell Res. 1994 Oct;214(2):459-64
7925641
J Bone Miner Res. 1999 Jul;14(7):1239-49
10404027
Circulation. 1998 Mar 10;97(9):907-15
9521340
Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68
15688067
J Clin Invest. 1997 Jun 15;99(12):2814-6
9185501
J Cell Biochem. 2006 Sep 1;99(1):35-52
16823799
Methods Mol Med. 2007;139:31-66
18287663
Anat Rec A Discov Mol Cell Evol Biol. 2005 Dec;287(2):1205-12
16240445
J Appl Physiol (1985). 2004 Oct;97(4):1550-8; discussion 1549
15121739
J Vasc Surg. 2007 Jun;45 Suppl A:A33-8
17544022
Cancer Res. 2006 Jul 15;66(14):6928-35
16849536
Atherosclerosis. 2006 Oct;188(2):292-300
16325820
Circ Res. 1990 Jul;67(1):61-7
2114227
Ann N Y Acad Sci. 2008 Mar;1123:30-40
18375575
Dev Biol. 2007 Feb 1;302(1):256-66
17070513
Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2115-22
18787183
J Cell Biochem. 1999 Dec 1;75(3):492-504
10536371
Cardiovasc Res. 2001 Dec;52(3):372-86
11738054
Cardiovasc Pathol. 2007 Sep-Oct;16(5):283-90
17868879
Basic Res Cardiol. 2001 Feb;96(1):42-9
11215531
Cardiovasc Res. 1997 Dec;36(3):408-28
9534862
Biochem Biophys Res Commun. 2005 Jun 3;331(2):404-12
15850774
J Biol Chem. 2000 Dec 29;275(52):41092-9
10998418
Cardiovasc Res. 2002 Mar;53(4):952-62
11922905
Am J Physiol Renal Physiol. 2008 Nov;295(5):F1463-71
18753297
Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):77-83
15514205