Interstitial flow induces MMP-1 expression and vascular SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism.

The migration of vascular smooth muscle cells (SMCs) and fibroblasts into the intima after vascular injury is a central process in vascular lesion formation. The elevation of transmural interstitial flow is also observed after damage to the vascular endothelium. We have previously shown that interstitial flow upregulates matrix metalloproteinase-1 (MMP-1) expression, which in turn promotes SMC and fibroblast migration in collagen I gels. In this study, we investigated further the mechanism of flow-induced MMP-1 expression. An ERK1/2 inhibitor PD-98059 completely abolished interstitial flow-induced SMC migration and MMP-1 expression. Interstitial flow promoted ERK1/2 phosphorylation, whereas PD-98059 abolished flow-induced activation. Silencing ERK1/2 completely abolished MMP-1 expression and SMC migration. In addition, interstitial flow increased the expression of activator protein-1 transcription factors (c-Jun and c-Fos), whereas PD-98059 attenuated flow-induced expression. Knocking down c-jun completely abolished flow-induced MMP-1 expression, whereas silencing c-fos did not affect MMP-1 expression. Taken together, our data indicate that interstitial flow induces MMP-1 expression and SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism and suggest that interstitial flow, ERK1/2 MAPK, c-Jun, and MMP-1 may play important roles in SMC migration and neointima formation after vascular injury.

[1]  V. Rizzo.  Enhanced interstitial flow as a contributing factor in neointima formation: (shear) stressing vascular wall cell types other than the endothelium. , 2009, American journal of physiology. Heart and circulatory physiology.

[2]  P. Lin,et al.  Lactosylceramide promotes cell migration and proliferation through activation of ERK1/2 in human aortic smooth muscle cells. , 2009, American journal of physiology. Heart and circulatory physiology.

[3]  J. Tarbell,et al.  Interstitial flow promotes vascular fibroblast, myofibroblast, and smooth muscle cell motility in 3-D collagen I via upregulation of MMP-1. , 2009, American journal of physiology. Heart and circulatory physiology.

[4]  Yizheng Wang,et al.  Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis , 2009, Molecular and Cellular Biology.

[5]  P. Lin,et al.  Chlorotyrosine promotes human aortic smooth muscle cell migration through increasing superoxide anion production and ERK1/2 activation. , 2008, Atherosclerosis.

[6]  M. Hetman,et al.  Requirement of 3-Phosphoinositide-Dependent Protein Kinase-1 for BDNF-Mediated Neuronal Survival , 2008, The Journal of Neuroscience.

[7]  Anthony J. Muslin.  MAPK signalling in cardiovascular health and disease: molecular mechanisms and therapeutic targets. , 2008, Clinical science.

[8]  M. Clark,et al.  Regulation of c-fos, c-jun and c-myc Gene Expression by Angiotensin II in Primary Cultured Rat Astrocytes: Role of ERK1/2 MAP Kinases , 2008, Neurochemical Research.

[9]  M. Li,et al.  Activating transcription factor 3 up-regulated by c-Jun NH2-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons , 2008, Neuroscience.

[10]  M. Feldman,et al.  IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-β, NF-κB, and AP-1 activation , 2007 .

[11]  M. Swartz,et al.  Interstitial flow and its effects in soft tissues. , 2007, Annual review of biomedical engineering.

[12]  John M Tarbell,et al.  Effects of fluid shear stress on adventitial fibroblast migration: implications for flow-mediated mechanisms of arterialization and intimal hyperplasia. , 2007, American journal of physiology. Heart and circulatory physiology.

[13]  J. Tarbell,et al.  Mechanotransduction and the glycocalyx , 2006, Journal of internal medicine.

[14]  Tom Shemesh,et al.  Focal adhesions as mechanosensors: a physical mechanism. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Yan Huang,et al.  Pioglitazone inhibits MMP-1 expression in vascular smooth muscle cells through a mitogen-activated protein kinase-independent mechanism. , 2005, Atherosclerosis.

[16]  J. Chung,et al.  Heat shock-induced matrix metalloproteinase (MMP)-1 and MMP-3 are mediated through ERK and JNK activation and via an autocrine interleukin-6 loop. , 2004, The Journal of investigative dermatology.

[17]  A. Rivard,et al.  Inhibition of Vascular Smooth Muscle Cell Proliferation and Neointimal Formation in Injured Arteries by a Novel, Oral Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Inhibitor , 2004, Circulation.

[18]  Y. Fung,et al.  Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. , 2004, Microvascular research.

[19]  M. Humbert,et al.  Cellular and molecular pathobiology of pulmonary arterial hypertension. , 2004, Journal of the American College of Cardiology.

[20]  J. Blenis,et al.  ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions , 2004, Microbiology and Molecular Biology Reviews.

[21]  D. Wakefield,et al.  UVB-elicited induction of MMP-1 expression in human ocular surface epithelial cells is mediated through the ERK1/2 MAPK-dependent pathway. , 2003, Investigative ophthalmology & visual science.

[22]  U. Shankavaram,et al.  Differential Regulation of Lipopolysaccharide-Induced Monocyte Matrix Metalloproteinase (MMP)-1 and MMP-9 by p38 and Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinases , 2003, The Journal of Immunology.

[23]  M. Gorospe,et al.  Tumor Promoter Arsenite Stimulates Histone H3 Phosphoacetylation of Proto-oncogenes c-fos and c-jun Chromatin in Human Diploid Fibroblasts* , 2003, The Journal of Biological Chemistry.

[24]  S. Meloche,et al.  Role of p44/p42 MAP Kinase in the Age-Dependent Increase in Vascular Smooth Muscle Cell Proliferation and Neointimal Formation , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[25]  A. Utani,et al.  Activation of p38 MAPK suppresses matrix metalloproteinase-1 gene expression induced by platelet-derived growth factor , 2003, Archives of Dermatological Research.

[26]  Jiahuai Han,et al.  Activation of p38α MAPK Enhances Collagenase-1 (Matrix Metalloproteinase (MMP)-1) and Stromelysin-1 (MMP-3) Expression by mRNA Stabilization* , 2002, The Journal of Biological Chemistry.

[27]  J. Tarbell,et al.  Flow through internal elastic lamina affects shear stress on smooth muscle cells (3D simulations). , 2002, American journal of physiology. Heart and circulatory physiology.

[28]  C. Brinckerhoff,et al.  Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors , 2001, Arthritis Research & Therapy.

[29]  K. Malik,et al.  Cytosolic phospholipase A2 activation by the p38 kinase inhibitor SB203580 in rabbit aortic smooth muscle cells. , 2001, The Journal of pharmacology and experimental therapeutics.

[30]  M. Karin,et al.  AP-1 in cell proliferation and survival , 2001, Oncogene.

[31]  Jiahuai Han,et al.  p38 Mitogen-Activated Protein Kinase-Dependent Activation of Protein Phosphatases 1 and 2A Inhibits MEK1 and MEK2 Activity and Collagenase 1 (MMP-1) Gene Expression , 2001, Molecular and Cellular Biology.

[32]  J. Thyberg,et al.  The Synthetic Metalloproteinase Inhibitor Batimastat Suppresses Injury-Induced Phosphorylation of MAP Kinase ERK1/ERK2 and Phenotypic Modification of Arterial Smooth Muscle Cells in vitro , 2000, Journal of Vascular Research.

[33]  John M. Tarbell,et al.  Effect of Fluid Flow on Smooth Muscle Cells in a 3-Dimensional Collagen Gel Model , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[34]  P. Cohen,et al.  Specificity and mechanism of action of some commonly used protein kinase inhibitors , 2000 .

[35]  M. Brauchle,et al.  Independent role of p38 and ERK1/2 mitogen-activated kinases in the upregulation of matrix metalloproteinase-1. , 2000, Experimental cell research.

[36]  M. Horton,et al.  Smooth muscle cell matrix metalloproteinase production is stimulated via alpha(v)beta(3) integrin. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[37]  I. Zachary,et al.  Differential regulation of extracellular signal-regulated protein kinases (ERKs) 1 and 2 by cAMP and dissociation of ERK inhibition from anti-mitogenic effects in rabbit vascular smooth muscle cells. , 1999, The Biochemical journal.

[38]  G. T. Bowden,et al.  Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription , 1999, Oncogene.

[39]  I. Zachary,et al.  Platelet-derived growth factor-BB (PDGF-BB) regulation of migration and focal adhesion kinase phosphorylation in rabbit aortic vascular smooth muscle cells: roles of phosphatidylinositol 3-kinase and mitogen-activated protein kinases. , 1999, Cardiovascular research.

[40]  M. Aoyagi,et al.  Immunolocalization of matrix metalloproteinases in rabbit carotid arteries after balloon denudation , 1998, Histochemistry and Cell Biology.

[41]  L. Cheng,et al.  Activation of mitogen-activated protein kinases (ERK/JNK) and AP-1 transcription factor in rat carotid arteries after balloon injury. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[42]  E. Haber,et al.  Mitogen-activated protein kinase phosphatase-1 in rat arterial smooth muscle cell proliferation. , 1996, The Journal of clinical investigation.

[43]  R. Alexander,et al.  Linoleic acid and its metabolites, hydroperoxyoctadecadienoic acids, stimulate c-Fos, c-Jun, and c-Myc mRNA expression, mitogen-activated protein kinase activation, and growth in rat aortic smooth muscle cells. , 1995, The Journal of clinical investigation.

[44]  J. Tarbell,et al.  Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells. , 1995, Journal of biomechanical engineering.

[45]  P. Chomczyński,et al.  Short technical reports. Modification of the TRI reagent procedure for isolation of RNA from polysaccharide- and proteoglycan-rich sources. , 1995, BioTechniques.

[46]  J. Tarbell,et al.  Vascular smooth muscle cell glycocalyx influences shear stress-mediated contractile response. , 2005, Journal of applied physiology.

[47]  R. Heller,et al.  Transcriptional control of matrix metalloproteinases and the tissue inhibitors of matrix metalloproteinases. , 1997, Critical reviews in eukaryotic gene expression.

[48]  A. Clowes,et al.  Regulation of vascular smooth muscle cell migration and proliferation in vitro and in injured rat arteries by a synthetic matrix metalloproteinase inhibitor. , 1996, Arteriosclerosis, thrombosis, and vascular biology.