Thrombospondin 1,Fibronectin,and Vitronectin are Differentially Dependent Upon RAS,ERK1/2,and p38 for Induction of Vascular Smooth Muscle Cell Chemotaxis
Restricted accessOtherFirst published online January, 2011
Thrombospondin 1,Fibronectin,and Vitronectin are Differentially Dependent Upon RAS,ERK1/2,and p38 for Induction of Vascular Smooth Muscle Cell Chemotaxis
Background: Thrombospondin 1 (TSP-1), fibronectin (Fn), and vitronectin (Vn) promote vascular smooth muscle cell (VSMC) chemotaxis through a variety of second messenger systems, including Ras, ERK1/2, and p38. Hypothesis: Ras, ERK1/2, and p38 differentially affect TSP-1-, Fn-, and Vn-induced VSMC chemotaxis. Methods: Bovine VSMCs were transfected with Ras N17 or treated with the following inhibitors: a farnesyl protein transferase (FPT) inhibitor, PD098059 (ERK1/2 inhibitor), or SB202190 (p38 inhibitor). Thrombospondin 1, Fn, and Vn were used as chemoattractants. Results were analyzed by analysis of variance (ANOVA) with post hoc testing (P < .05). Results: Ras N17 transfection or FPT inhibitor treatment inhibited TSP-1-, Fn-, and Vn-induced chemotaxis. PD098059 or SB202190 resulted in more inhibition of VSMC migration to TSP-1 than to Fn or Vn. Conclusions: Ras appears equally relevant in the signal transduction pathways of TSP-1-, Fn-, and Vn-induced VSMC chemotaxis. Thrombospondin 1-induced migration is more dependent upon ERK1/2 and p38 than Fn- or Vn-included migration.
Nelson PR, Yamamura S., Kent KCExtracellular matrix proteins are potent agonists of human smooth muscle cell migration. J Vasc Surg. 1996;24(1):25-33.
5.
van Aken BE, Seiffert D., Thinnes T., Loskutoff DJLocalization of vitronectin in the normal and atherosclerotic human vessel wall. Histochem Cell Biol. 1997;107(4):313-320.
Roth JJ, Gahtan V., Brown JL, et al. Thrombospondin-1 is elevated with both intimal hyperplasia and hypercholesterolemia. J Surg Res. 1998;74(1):11-16.
8.
Gahtan V., Wang XJ, Willis AI, Tuszynski GP, Sumpio BEThrombospondin-1 regulation of smooth muscle cell chemotaxis is extracellular signal-regulated protein kinases 1/2 dependent. Surgery. 1999;126(2):203-207.
9.
Fuse S., Esemuede N., Yamaguchi MS, et al. The role of G proteins in thrombospondin-1-induced vascular smooth muscle cell migration. Surgery. 2008 ;144(1):86-92.
10.
Esemuede N. , Lee T., Maier KG, et al. Lovastatin inhibits thrombospondin-1-induced smooth muscle cell chemotaxis. J Surg Res. Epub2009 (IN PRESS).
11.
Wang XJ, Willis AI, Kito H., et al. Thrombospondin-1 induces p38 activation in vascular smooth muscle cells. FASEB J.1999; 13(3):A436.
12.
Wang XJ, Maier K., Willis AI, et al. Thrombospondin-1-induced migration is functionally dependent upon focal adhesion kinase. Vascular and Endovascular Surgery . 2008;42(3): 256-262.
13.
Lee TS, Nesselroth SM, Olson ET, et al. Thrombospondin-1-induced vascular smooth muscle cell chemotaxis: The role of the type 3 repeat and carboxyl terminal domains. J Cell Biochem. 2003;89(3):500-506.
14.
Campbell SL , Khosravi-Far R., Rossman KL, Clark GJ, Der CJIncreasing complexity of Ras signaling. Oncogene. 1998; 17(11):1395-1413.
Willis AI, Fuse S., Wang XJ, et al. Inhibition of phosphatidylinositol-3-kinase and protein kinase C attenuates extracellular matrix protein-induced vascular smooth muscle cell chemotaxis. J Vasc Surg. 2000;31(6):1160-1167.
17.
Seymour K., Han X., Sadowitz B., et al. Differential effect of nitric oxide on thrombospondin-1-, PDGF-, and fibronectin-induced migration of vascular smooth muscle cells. Am J Surg. 2010; Accepted (IN PRESS).
18.
Maier KG, Sadowitz B., Cullen S., Han X., Gahtan V.Thrombospondin-1-induced vascular smooth muscle cell migration is dependent on the hyaluronic acid receptor CD44. The American Journal of Surgery.2009;198(5):664-669.
19.
Shirai H., Autieri M., Eguchi S. Small GTP-binding proteins and mitogen-activated protein kinases as promising therapeutic targets of vascular remodeling. Curr Opin Nephrol Hypertens. 2007;16(2):111-115.
20.
Li C., Hu Y., Sturm G., Xu Q.Ras/Rac-dependent activation of p38 mitogen-activated protein kinases in smooth muscle cells stimulated by cyclic strain stress. Arterioscler Thromb Vasc Biol. 2000;20(3):e1-e9.
21.
Koyama H., Olson NE, Dastvan FF, Reidy MACell replication in the arterial wall: activation of signaling pathway following an in vivo injury. Circ Res. 1998;82(6):713-721.
22.
Graf K., Xi XP, Yang D., Fleck E., Hsueh WA, Law REMitogen-activated protein kinase activation is involved in platelet-derived growth factor-directed migration by vascular smooth muscle cells. Hypertension. 1997;29(1pt2):334-339.
23.
Nelson PR, Yamamura S., Mureebe L., Itoh H., Kent KCSmooth muscle cell migration and proliferation are mediated by distinct phases of activation of the intracellular messenger mitogen-activated protein kinase . J Vasc Surg. 1998;27(1):117-125.
24.
Pukac L., Huangpu J., Karnovsky MJPlatelet-derived growth factor-BB, insulin-like growth factor-1, and phorbol ester activate different signaling pathways for stimulation of vascular smooth muscle cell migration. Exp Cell Res. 1998;242(2):548-560.
25.
Klemke RL, Cai S., Giannini AL, Gallagher PJ, de Lanerolle P., Cheresh DARegulation of cell motility by mitogen-activated protein kinase. J Cell Biol. 1997;137(2):481-492.
26.
Servant MJ, Giasson E., Meloche S.Inhibition of growth factor-induced protein synthesis by a selective MEK inhibitor in aortic smooth muscle cells. J Biol Chem. 1996;271(27):16047-16052.
27.
Di Luozzo G. , Pradhan S., Dhadwal AK, Chen A., Ueno H., Sumpio BENicotine induces mitogen-activated protein kinase dependent vascular smooth muscle cell migration. Atherosclerosis . 2005;178(2):271-277.
28.
Itoh H., Nelson PR, Kaiura TL, Kent KCDistinct signaling pathways mediate extracellular matrix protein versus platelet-derived growth factor-induced smooth muscle cell migration. Surg Forum . 1998;XLIX(2):311.
29.
He Q., LaPointe M.Interleukin-1beta regulates the human brain natriuretic peptide promoter via Ca2+-dependent protein kinase pathways. Hypertension. 2000;35[part2]:292-296.
30.
Awane M., Andres PG, Li DJ, Reinecker HCNF-{kappa}B-inducing kinase is a common mediator of IL-17, TNF-{alpha}-, and IL-1-{beta}-induced chemokine promoter activation in intestinal epithelial cells. J Immunol. 1999;162(9):5337-5344.
31.
Landry J., Huot J.Modulation of actin dynamics during stress and physiological stimulation by a signaling pathway involving p38 MAP kinase. Biochem Cell Biol. 1995;73(9-10):703-707.
32.
Li S., Tanaka H., Wang HH, et al. Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation . American Journal of Physiology - Heart and Circulatory Physiology . 2006;291(3):H1262-H1272.
