Deletion of discoidin domain receptor 2 does not affect smooth muscle cell adhesion, migration, or proliferation in response to type I collagen

2012 ◽  
Vol 21 (3) ◽  
pp. 214-218 ◽  
Author(s):  
Guangpei Hou ◽  
David Wang ◽  
Michelle P. Bendeck
Keyword(s):  
Smooth Muscle ◽  
Cell Adhesion ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Type I Collagen ◽  
Type I ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2

Induction of vascular smooth muscle cell tenascin-C gene expression by denatured type I collagen is dependent upon a beta3 integrin-mediated mitogen-activated protein kinase pathway and a 122-base pair promoter element

1999 ◽  
Vol 112 (4) ◽  
pp. 435-445 ◽  
Author(s):  
P.L. Jones ◽  
F.S. Jones ◽  
B. Zhou ◽  
M. Rabinovitch
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Type I Collagen ◽  
Type I ◽  
C Protein ◽  
Tenascin C ◽  
Beta3 Integrin

Tenascin-C is an extracellular matrix glycoprotein, the expression of which is upregulated in remodeling arteries. In previous studies we showed that the presence of tenascin-C alters vascular smooth muscle cell shape and amplifies their proliferative response by promoting growth factor receptor clustering and phosphorylation. Moreover, we demonstrated that denatured type I collagen induces smooth muscle cell tenascin-C protein production via beta3 integrins. In the present study, we examine the pathway by which beta3 integrins stimulate expression of tenascin-C, and define a promoter sequence that is critical for its induction. On native collagen, A10 smooth muscle cells adopt a stellate morphology and produce low levels of tenascin-C mRNA and protein, whereas on denatured collagen they spread extensively and produce high levels of tenascin-C mRNA and protein, which is incorporated into an elaborate extracellular matrix. Increased tenascin-C synthesis on denatured collagen is associated with elevated protein tyrosine phosphorylation, including activation of extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2). beta3 integrin function-blocking antibodies attenuate ERK1/2 activation and tenascin-C protein synthesis. Consistent with these findings, treatment with the specific MEK inhibitor, PD 98059, results in suppression of tenascin-C protein synthesis. To investigate whether beta3 integrin-dependent activation of ERK1/2 regulates the tenascin-C promoter, we transfected A10 cells with a full-length (approx. 4 kb) mouse tenascin-C gene promoter-chloramphenicol acetyltransferse reporter construct and showed that, relative to native collagen, its activity is increased on denatured collagen. Next, to identify regions of the promoter involved, we examined a series of tenascin-C promoter constructs with 5′ deletions and showed that denatured collagen-dependent promoter activity was retained by a 122-base pair element, located -43 to -165 bp upstream of the RNA start site. Activation of this element was suppressed either by blocking beta3 integrins, or by preventing ERK1/2 activation. These observations demonstrate that smooth muscle cell binding to beta3 integrins activates the mitogen activated protein kinase pathway, which is required for the induction of tenascin-C gene expression via a potential extracellular matrix response element in the tenascin-C gene promoter. Our data suggest a mechanism by which remodeling of type I collagen modulates tenascin-C gene expression via a beta3 integrin-mediated signaling pathway, and as such represents a paradigm for vascular development and disease whereby smooth muscle cells respond to perturbations in extracellular matrix composition by altering their phenotype and patterns of gene expression.

scholarly journals Matrix Metalloproteinase and αvβ3 Integrin–Dependent Vascular Smooth Muscle Cell Invasion Through a Type I Collagen Lattice

2000 ◽  
Vol 20 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Shigeru Kanda ◽  
Masafumi Kuzuya ◽  
Miguel A. Ramos ◽  
Teruhiko Koike ◽  
Kohichiro Yoshino ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Cell Invasion ◽  
Type I Collagen ◽  
Type I ◽  
Αvβ3 Integrin

An In Vitro Study of Nano-fiber Polymers for Guided Vascular Regeneration

2001 ◽  
Vol 711 ◽  
Author(s):  
Derick C. Miller ◽  
Anil Thapa ◽  
Karen M. Haberstroh ◽  
Thomas J. Webster
Keyword(s):  
Smooth Muscle ◽  
Cell Adhesion ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Surrounding Tissue ◽  
Arterial Smooth Muscle Cell ◽  
Arterial Smooth Muscle ◽  
Cell Functions ◽  
Fiber Dimensions

ABSTRACTBiomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also the dimensions of the associated nano-structured extra-cellular matrix (ECM) components. The goal of this research was to use these ideals to develop a synthetic, nano-structured, polymeric biomaterial that has cytocompatible and mechanical behaviors similar to that of natural vascular tissue. In a novel manner, poly-lactic acid/polyglycolic acid (PLGA) (50/50 wt.% mix) and polyurethane were separately synthesized to possess a range of fiber dimensions in the micron and nanometer regime. Preliminary results indicated that decreasing fiber diameter on both PLGA and PU enhanced arterial smooth muscle cell adhesion; specifically, arterial smooth muscle cell adhesion increased 23% when PLGA fiber dimensions decreased from 500 to 50 nm and increased 76% on nano-structured, compared to conventional structured, polyurethane. However, nano-structured PLGA decreased endothelial cell adhesion by 52%, whereas adhesion of these same cells was increased by 50% on polyurethane. For these reasons, the present in vitro study provides the first evidence that polymer fiber dimensions can be used to selectively control cell functions for vascular prosthesis.

scholarly journals Role of c-Abl tyrosine kinase in smooth muscle cell migration

2014 ◽  
Vol 306 (8) ◽  
pp. C753-C761 ◽  
Author(s):  
Rachel A. Cleary ◽  
Ruping Wang ◽  
Omar Waqar ◽  
Harold A. Singer ◽  
Dale D. Tang
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Leading Edge ◽  
Actin Dynamics ◽  
Cell Edge ◽  
Smooth Muscle Cell Migration

c-Abl is a nonreceptor protein tyrosine kinase that has a role in regulating smooth muscle cell proliferation and contraction. The role of c-Abl in smooth muscle cell migration has not been investigated. In the present study, c-Abl was found in the leading edge of smooth muscle cells. Knockdown of c-Abl by RNA interference attenuated smooth muscle cell motility as evidenced by time-lapse microscopy. Furthermore, the actin-associated proteins cortactin and profilin-1 (Pfn-1) have been implicated in cell migration. In this study, cell adhesion induced cortactin phosphorylation at Tyr-421, an indication of cortactin activation. Phospho-cortactin and Pfn-1 were also found in the cell edge. Pfn-1 directly interacted with cortactin in vitro. Silencing of c-Abl attenuated adhesion-induced cortactin phosphorylation and Pfn-1 localization in the cell edge. To assess the role of cortactin/Pfn-1 coupling, we developed a cell-permeable peptide. Treatment with the peptide inhibited the interaction of cortactin with Pfn-1 without affecting cortactin phosphorylation. Moreover, treatment with the peptide impaired the recruitment of Pfn-1 to the leading edge and cell migration. Finally, β1-integrin was required for the recruitment of c-Abl to the cell edge. Inhibition of actin dynamics impaired the spatial distribution of c-Abl. These results suggest that β1-integrin may recruit c-Abl to the leading cell edge, which may regulate cortactin phosphorylation in response to cell adhesion. Phosphorylated cortactin may facilitate the recruitment of Pfn-1 to the cell edge, which promotes localized actin polymerization, leading edge formation, and cell movement. Conversely, actin dynamics may strengthen the recruitment of c-Abl to the leading edge.

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