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The Role of Smoothened and Hh Signaling in Neovascularization

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The Smoothened Receptor in Cancer and Regenerative Medicine

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 16))

Abstract

New vessel formation plays a key role not only in physiological processes such as embryonic development and wound repair but also during several pathological situations. In this respect, favoring neovascularization represents a promising therapeutic approach that would allow inducing tissue repair. Among the candidate proteins able to modulate neovascularization, evidence show that the administration of recombinant hedgehog (Hh) protein, gene, or cell therapy based on Hh transfer or using extracellular vesicles as vectors enhance new vessel formation. Here, we summarized the role of Hh pathway on angiogenesis and its therapeutic potential during myocardial infarction and diabetes.

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Abbreviations

AMPK:

AMP-activated protein kinase

Ang(1, 2):

Angiopoietin(1, 2)

CECs:

Circulating endothelial cells

Dhh:

Desert hedgehog

ECM:

Extracellular matrix

eNOS:

Endothelial nitric oxide synthase

ERK:

Extracellular signal-regulated kinase

FAK:

Focal adhesion kinase

FGF:

Fibroblast growth factor

Gli(1, 2, 3):

Glioma-associated oncogenes(1, 2, 3)

GPCR:

G-protein-coupled receptors

Hh:

Hedgehog

HIF-1:

Hypoxia-inducible factor-1

Ihh:

Indian hedgehog

iNOS:

Inducible nitric oxide synthase

JNK:

c-Jun N-terminal kinase

LGR5:

Leucine-rich repeat G-protein-coupled receptor 5

LMPs:

Lymphocytic microparticles

MAPK:

Mitogen-activated protein kinase

miRs:

MicroRNAs

MPs:

Microparticles

MPsShh+ :

Microparticles expressing sonic hedgehog

mRNA:

Messenger RNA

NO:

Nitric oxide

PDGF:

Platelet-derived growth factor

PECAM-1:

Platelet-endothelial cell-adhesion molecule-1

phShh:

Plasmid encoding the sonic hedgehog human gene

PI3K:

Phosphatidylinositol 3-kinase

PKC:

Protein kinase C

Ptc:

Patched

ROCK:

Rho-associated protein kinase

ROS:

Reactive oxygen species

SDF-1:

Stromal cell-derived factor-1

Shh:

Sonic hedgehog

Smo:

Smoothened

TGF-β:

Transforming growth factor β

TSP1:

Thrombospondin1

TYMP:

Thymidine phosphorylase

VE-cadherin:

Vascular endothelial cadherin

VEGF:

Vascular endothelial growth factor

VEGFR(−1, −2):

Vascular endothelial growth factor receptor(−1, −2)

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Authors and Affiliations

  1. INSERM UMR1063, Stress oxydant et pathologies métaboliques, Angers, France

    Raffaella Soleti, Ramaroson Andriantsitohaina & Maria Carmen Martínez

  2. Centre Hospitalier Universitaire d’Angers, Angers, France

    Ramaroson Andriantsitohaina

  3. Institut de Biologie en Santé, 4 rue Larrey, Angers, France

    Maria Carmen Martínez

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  1. Raffaella Soleti
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  2. Ramaroson Andriantsitohaina
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  3. Maria Carmen Martínez
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Correspondence to Maria Carmen Martínez .

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  1. Institute of Neurosciences Paris-Saclay (Neuro-PSI), National Centre for Scientific Research, Gif-Yvette, France

    Martial Ruat

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Soleti, R., Andriantsitohaina, R., Martínez, M.C. (2014). The Role of Smoothened and Hh Signaling in Neovascularization. In: Ruat, M. (eds) The Smoothened Receptor in Cancer and Regenerative Medicine. Topics in Medicinal Chemistry, vol 16. Springer, Cham. https://doi.org/10.1007/7355_2014_70

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