Characterisation of PDGF-BB:PDGFRβ signalling pathways in human brain pericytes: evidence of disruption in Alzheimer's disease.

Alzheimer Disease / metabolism Becaplermin / metabolism Brain / metabolism Humans Pericytes Receptor, Platelet-Derived Growth Factor beta / metabolism

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
17 03 2022
Historique:
received: 28 07 2021
accepted: 17 02 2022
entrez: 18 3 2022
pubmed: 19 3 2022
medline: 6 4 2022
Statut: epublish

Résumé

Platelet-derived growth factor-BB (PDGF-BB):PDGF receptor-β (PDGFRβ) signalling in brain pericytes is critical to the development, maintenance and function of a healthy blood-brain barrier (BBB). Furthermore, BBB impairment and pericyte loss in Alzheimer's disease (AD) is well documented. We found that PDGF-BB:PDGFRβ signalling components were altered in human AD brains, with a marked reduction in vascular PDGFB. We hypothesised that reduced PDGF-BB:PDGFRβ signalling in pericytes may impact on the BBB. We therefore tested the effects of PDGF-BB on primary human brain pericytes in vitro to define pathways related to BBB function. Using pharmacological inhibitors, we dissected distinct aspects of the PDGF-BB response that are controlled by extracellular signal-regulated kinase (ERK) and Akt pathways. PDGF-BB promotes the proliferation of pericytes and protection from apoptosis through ERK signalling. In contrast, PDGF-BB:PDGFRβ signalling through Akt augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB signalling to stabilise the cerebrovasculature in AD.

Identifiants

DOI: 10.1038/s42003-022-03180-8 PMID: 35301433 PMC: PMC8931009
pubmed: 35301433
doi: 10.1038/s42003-022-03180-8
pii: 10.1038/s42003-022-03180-8
pmc: PMC8931009
doi:

Substances chimiques

Becaplermin 1B56C968OA
Receptor, Platelet-Derived Growth Factor beta EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

235

Informations de copyright

© 2022. The Author(s).

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Auteurs

Leon C D Smyth (LCD)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Centre for Free Radical Research, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
Center for Brain Immunology and Glia, Department of Pathology and Immunology, Washington University in St Louis, Missouri, USA.
ORCID: 0000-0001-9861-3574

Blake Highet (B)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.

Deidre Jansson (D)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Psychiatry and Behavioural Sciences, University of Washington, Seattle, Washington, USA.
ORCID: 0000-0001-9757-8682

Jane Wu (J)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.

Justin Rustenhoven (J)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Center for Brain Immunology and Glia, Department of Pathology and Immunology, Washington University in St Louis, Missouri, USA.

Miranda Aalderink (M)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Adelie Tan (A)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.

Susan Li (S)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
ORCID: 0000-0001-5238-514X

Rebecca Johnson (R)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Natacha Coppieters (N)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Laboratory of Nervous System Disorders and Therapy, GIGA-Neurosciences Research Centre, University of Liège, 4000, Liège, Belgium.

Renee Handley (R)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
School of Biological Sciences, University of Auckland, Auckland, New Zealand.

Pritika Narayan (P)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
ORCID: 0000-0002-8713-1470

Malvindar K Singh-Bains (MK)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.

Patrick Schweder (P)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Auckland City Hospital, 2 Park Road, Auckland, 1023, New Zealand.

Clinton Turner (C)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Auckland City Hospital, 2 Park Road, Auckland, 1023, New Zealand.

Edward W Mee (EW)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Auckland City Hospital, 2 Park Road, Auckland, 1023, New Zealand.

Peter Heppner (P)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Auckland City Hospital, 2 Park Road, Auckland, 1023, New Zealand.

Jason Correia (J)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Auckland City Hospital, 2 Park Road, Auckland, 1023, New Zealand.

Thomas I-H Park (TI)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
ORCID: 0000-0002-7995-8865

Maurice A Curtis (MA)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.

Richard L M Faull (RLM)

Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.

Mike Dragunow (M)

Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand. m.dragunow@auckland.ac.nz.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. m.dragunow@auckland.ac.nz.
ORCID: 0000-0003-1711-1631

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Characterisation of PDGF-BB:PDGFRβ signalling...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteur de croissance dérivé des plaquettes › Protéines proto-oncogènes c-sis › Bécaplermine › Characterisation of PDGF-BB:PDGFRβ signalling...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Characterisation of PDGF-BB:PDGFRβ signalling...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Characterisation of PDGF-BB:PDGFRβ signalling...
questionsmedicales.fr › Structures de l'embryon › Feuillets embryonnaires › Mésoderme › Péricytes › Characterisation of PDGF-BB:PDGFRβ signalling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs aux facteurs de croissance dérivés des plaquettes › Récepteur au PDGF bêta › Characterisation of PDGF-BB:PDGFRβ signalling...