Substrate stiffening promotes VEGF-A functions via the PI3K/Akt/mTOR pathway.

Biomechanical Phenomena Cell Line Cell Movement Cell Proliferation Elasticity Endothelial Cells / cytology Epithelial Cells / cytology Gene Expression Regulation Humans Mechanotransduction, Cellular / genetics Models, Biological Neovascularization, Pathologic / genetics Phosphatidylinositol 3-Kinases / genetics Primary Cell Culture Proto-Oncogene Proteins c-akt / genetics Retinal Pigment Epithelium / cytology TOR Serine-Threonine Kinases / genetics Vascular Endothelial Growth Factor A / genetics
AMD Angiogenesis Contraction Endothelial cell Proliferation RPE Rigidity

Journal

Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516

Informations de publication

Date de publication:
01 01 2022
Historique:
received: 03 11 2021
accepted: 09 11 2021
pubmed: 26 11 2021
medline: 13 1 2022
entrez: 25 11 2021
Statut: ppublish

Résumé

While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR signaling pathway. This pathway is activated on stiffer substrates, is amplified by VEGF-A stimulation, and correlates with enhanced endothelial cell (EC) proliferation, contraction, pro-angiogenic secretion, and capillary-like tube formation. In the settings of advanced age-related macular degeneration, characterized by EC and retinal pigment epithelial (RPE)-mediated angiogenesis, these data implicate substrate stiffness as a novel causative mechanism and Akt/mTOR inhibition as a novel therapeutic pathway.

Identifiants

DOI: 10.1016/j.bbrc.2021.11.030 PMID: 34823219 PMC: PMC8785232
pubmed: 34823219
pii: S0006-291X(21)01541-2
doi: 10.1016/j.bbrc.2021.11.030
pmc: PMC8785232
mid: NIHMS1759002
pii:
doi:

Substances chimiques

VEGFA protein, human 0
Vascular Endothelial Growth Factor A 0
MTOR protein, human EC 2.7.1.1
Proto-Oncogene Proteins c-akt EC 2.7.11.1
TOR Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

27-33

Subventions

Organisme : NIH HHS
ID : DP2 OD006649
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL123522
Pays : United States
Organisme : CIHR
ID : 143327
Pays : Canada

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Amjad Husain (A)

Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA; Innovation and Incubation Centre for Entrepreneurship, IISER, Bhopal, MP, 462066, India; Centre for Science and Society, IISER, Bhopal, MP, 462066, India.

Arogya Khadka (A)

Schepens Eye Research Institute at Massachusetts Eye and Ear, Boston, MA, 02114, USA.

Allen Ehrlicher (A)

Department of Bioengineering, McGill University, Montreal, H3A0C3, Canada.

Magali Saint-Geniez (M)

Schepens Eye Research Institute at Massachusetts Eye and Ear, Boston, MA, 02114, USA.

Ramaswamy Krishnan (R)

Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. Electronic address: rkrishn2@bidmc.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiques › Phénomènes mécaniques › Phénomènes biomécaniques › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Phénomènes physiques › Phénomènes mécaniques › Élasticité › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Cellules › Cellules épithéliales › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Mécanotransduction cellulaire › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Métaplasie › Néovascularisation pathologique › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes c-akt › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Organes des sens › Oeil › Rétine › Épithélium pigmentaire de la rétine › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Substrate stiffening promotes VEGF-A functions...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines angiogéniques › Facteurs de croissance endothéliale vasculaire › Facteur de croissance endothéliale vasculaire de type A › Substrate stiffening promotes VEGF-A functions...