Inhibition of FGF-2-Mediated Chemotaxis of Murine Brain Capillary Endothelial Cells by Cyclic RGDfV Peptide through Blocking the Redistribution of c-Src into Focal Adhesions

Shono, Takefumi; Mochizuki, Yoshinari; Kanetake, Hiroshi; Kanda, Shigeru

doi:10.1006/excr.2001.5276

Cited by 20 publications

(16 citation statements)

References 43 publications

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“…We used the cRGDfV peptide because it was shown to be inhibitory for ␣V␤3 (IC 50 ϭ50 M) matrix binding and used for rodent cells. 28,29 Also, other components, such as blocking antibodies, have been shown to cause vasodilation, 30,31 which could have confounded our studies.…”

Section: Discussionmentioning

confidence: 99%

αV Integrins Are Necessary for Eutrophic Inward Remodeling of Small Arteries in Hypertension

Heerkens

Shaw²,

Ryding³

et al. 2006

Hypertension

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Abstract-Human essential hypertension is characterized by eutrophic remodeling of small arteries, with little evidence of hypertrophy. Likewise, vessels of young hypertensive TGR(mRen2)27 animals have undergone similar structural alterations. The role of integrins in resistance arteries of TGR(mRen2)27 during the eutrophic-remodeling process was examined as blood pressure rose. Initially, 8 ␣ and 3 ␤ integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only ␣V was significantly raised. In conjunction, we confirmed elevated integrin ␣V protein levels in TGR(mRen2)27 rat arteries and localization to the media using immunofluorescence. ␤1 and ␤3, but not ␤5 integrin subunits were coprecipitated with integrin ␣V and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of ␣V␤3 abolished remodeling but enhanced growth, indicating that hypertrophy supervened as a response to hypertensioninduced increases in wall stress. We have established that the only upregulated integrin, the ␣V subunit of integrin ␣V␤3, has a crucial role in the hypertensive remodeling process of TGR(mRen2)27 rat resistance arteries. During hypertensive remodeling, functions of specific ␣V␤3-extracellular matrix interactions are likely to allow vascular smooth muscle cell-length autoregulation, which includes a migratory process, to maintain a narrowed lumen after a prolonged constricted state. A lthough the causes of high blood pressure may vary, sustained hypertension is associated with changes in cardiovascular structure. 1 These can be seen from the left ventricle down to the resistance vessels, and there is a strong relationship between left ventricular mass and small artery structure. 2,3 Resistance to blood flow is provided by arteries with an internal diameter (ID) of Յ300 m, 4 and in subcutaneous vessels, there is clear evidence for an increased media thickness:lumen diameter ratio in essential hypertension, which is proportional to the severity of the blood pressure. 1,5,6 Such findings appear to be representative of other vascular beds, with similar results being reported in the small intestine and the heart. 7,8 The nature of the structural change that is effected by hypertension is a rearrangement of the preexisting material in the vascular wall without a major hypertrophic response. 9 This has been termed eutrophic inward remodeling, which is initiated by vascular smooth muscle cell (VSMC)-length autoregulation. 10 Constriction causes shortening of VSMCs and a return to normal length after dissipation of the stimulus; however, prolonged constriction causes cells to increase in overlap. This functional adaptation to prolonged vasoconstriction is thought to occur because it is an energetically favored mechanism to preserve a reduced lumen diameter for long periods. 10 All models of hypertension appear to demonstrate eutrophic remodeling in small arteries, although to differing extents. ...

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Section: Discussionmentioning

confidence: 99%

αV Integrins Are Necessary for Eutrophic Inward Remodeling of Small Arteries in Hypertension

Heerkens

Shaw²,

Ryding³

et al. 2006

Hypertension

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“…Expression of a kinase-inactive c-Fes mutant interferes with FGF2-induced chemotaxis in endothelial cells [33]. Moreover, FGF2-mediated chemotaxis on fibronectincoated substrata can be attenuated by a v b 3 integrin inhibitors [34].…”

Section: Endothelial Cell Migrationmentioning

confidence: 99%

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Presta

Dell’Era

Mitola

et al. 2005

Cytokine & Growth Factor Reviews

1,130

870

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Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors. FGFs exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Their activity is modulated by a variety of free and extracellular matrix-associated molecules. Also, the cross-talk among FGFs, vascular endothelial growth factors (VEGFs), and inflammatory cytokines/chemokines may play a role in the modulation of blood vessel growth in different pathological conditions, including cancer. Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization. #

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“…Previous studies have demonstrated that the N-terminal region of Reelin binds ␣3␤1-integrin (Dulabon et al, 2000;Förster et al, 2002;Schmid et al, 2005). To test whether Reelin-integrin interactions may contribute to the presynaptic effects of Reelin, an integrin inhibitor peptide (Shono et al, 2001) was added to organotypic slice cultures of reeler hippocampi treated with recombinant Reelin (n ϭ 3 animals, one experiment per animal and condition). Our subsequent Western immunoblot analysis showed that the rescue effect of Reelin on SNAP25 was abolished in the presence of RGD motive-containing integrin inhibitor peptides, whereas addition of integrin inhibitor peptides to mock-treated tissue had no significant effect (Fig.…”

Section: Integrin Inhibitor Peptides Neutralize the Rescue Effect Of mentioning

confidence: 99%

Role for Reelin in Neurotransmitter Release

Hellwig¹,

Hack²,

Kowalski³

et al. 2011

J. Neurosci.

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The extracellular matrix molecule Reelin is known to control neuronal migration during development. Recent evidence suggests that it also plays a role in the maturation of postsynaptic dendrites and spines as well as in synaptic plasticity. Here, we aimed to address the question whether Reelin plays a role in presynaptic structural organization and function. Quantitative electron microscopic analysis of the number of presynaptic boutons in the stratum radiatum of hippocampal region CA1 did not reveal differences between wild-type animals and Reelin-deficient reeler mutant mice. However, additional detailed analysis showed that the number of presynaptic vesicles was significantly increased in CA1 synapses of reeler mutants. To test the hypothesis that vesicle fusion is altered in reeler, we studied proteins known to control transmitter release. SNAP25, a protein of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, was found to be significantly reduced in reeler mutants, whereas other SNARE complex proteins remained unaltered. Addition of recombinant Reelin to organotypic slice cultures of reeler hippocampi substantially rescued not only SNAP25 protein expression levels but also the number of vesicles per bouton area indicating a role for Reelin in presynaptic functions. Next, we analyzed paired-pulse facilitation, a presynaptic mechanism associated with transmitter release, and observed a significant decrease at CA1 synapses of reeler mutants when compared with wild-type animals. Together, these novel findings suggest a role for Reelin in modulating presynaptic release mechanisms.

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Inhibition of FGF-2-Mediated Chemotaxis of Murine Brain Capillary Endothelial Cells by Cyclic RGDfV Peptide through Blocking the Redistribution of c-Src into Focal Adhesions

Cited by 20 publications

References 43 publications

αV Integrins Are Necessary for Eutrophic Inward Remodeling of Small Arteries in Hypertension

αV Integrins Are Necessary for Eutrophic Inward Remodeling of Small Arteries in Hypertension

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Role for Reelin in Neurotransmitter Release

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