The TrkB-T1 receptor mediates BDNF-induced migration of aged cardiac microvascular endothelial cells by recruiting Willin.
Animals
Brain-Derived Neurotrophic Factor
/ metabolism
Cell Movement
Cells, Cultured
Cellular Senescence
Endothelial Cells
/ cytology
HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins
/ metabolism
Myocytes, Cardiac
/ cytology
Neovascularization, Physiologic
Rats
Receptor, trkB
/ genetics
Signal Transduction
BDNF-TrkB
Hippo pathway
Willin/FRMD6
cardiac microvascular endothelial cell aging
migration
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
04
05
2018
revised:
22
10
2018
accepted:
29
10
2018
pubmed:
23
1
2019
medline:
21
4
2020
entrez:
23
1
2019
Statut:
ppublish
Résumé
The mechanism of age-related decline in the angiogenic potential of the myocardium is not yet fully understood. Our previous report revealed that the aging of cardiac microvascular endothelial cells (CMECs) led to changes in their expression of receptor Trk isoforms: among the three isoforms (TrkB-FL, TrkB-T1 and TrkB-T2), only the truncated TrkB-T1 isoform continued to be expressed in aged CMECs, which led to decreased migration of CMECs in aging hearts. Thus far, how BDNF induces signalling through the truncated TrkB-T1 isoform in aged CMECs remains unclear. Here, we first demonstrated that aged CMECs utilize BDNF-TrkB-T1 signalling to recruit Willin as a downstream effector to further activate the Hippo pathway, which then promotes migration. These findings suggest that the aging process shifts the phenotype of aged CMECs that express TrkB-T1 receptors by transducing BDNF signals via the BDNF-TrkB-T1-Willin-Hippo pathway and that this change might be an important mechanism and therapeutic target of the dysfunctional cardiac angiogenesis observed in aged hearts.
Identifiants
pubmed: 30667167
doi: 10.1111/acel.12881
pmc: PMC6413668
doi:
Substances chimiques
Bdnf protein, mouse
0
Brain-Derived Neurotrophic Factor
0
Frmd6 protein, mouse
0
Intracellular Signaling Peptides and Proteins
0
Receptor, trkB
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
e12881Subventions
Organisme : Major Research plan of the National Natural Science Foundation of China-Key program
ID : 91649203
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81670236
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81470433
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81170324
Pays : International
Organisme : National Key R&D Program of China
ID : 2016YFE0204700
Pays : International
Organisme : National Key R&D Program of China
ID : 2017YFA0103302
Pays : International
Organisme : Science and Technology Planning Project of Guangdong Province
ID : 2015B020211010
Pays : International
Organisme : Research grant of the Department of Education of Guangdong
ID : 2012gjhz0003
Pays : International
Organisme : Guangdong Natural Science Funds for Distinguished Young Scholar
ID : 2014A030306011
Pays : International
Informations de copyright
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Références
Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H463-9
pubmed: 12730063
Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1902-9
pubmed: 22556331
Circ Res. 2012 Apr 27;110(9):1252-64
pubmed: 22539758
Head Neck. 2006 Nov;28(11):1018-27
pubmed: 16783828
Genes Dev. 1994 Aug 15;8(16):1875-87
pubmed: 7958863
Int J Mol Sci. 2013 May 13;14(5):10122-42
pubmed: 23670594
Cytokine Growth Factor Rev. 2012 Feb-Apr;23(1-2):15-24
pubmed: 22341689
Aging Cell. 2019 Apr;18(2):e12881
pubmed: 30667167
Cancer Cell. 2008 Mar;13(3):188-92
pubmed: 18328423
Oncogene. 2012 Jan 12;31(2):238-50
pubmed: 21666719
Curr Biol. 2002 Feb 5;12(3):217-20
pubmed: 11839274
J Physiol Pharmacol. 2010 Apr;61(2):133-9
pubmed: 20436213
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1880-5
pubmed: 25583515
J Clin Invest. 1998 Aug 15;102(4):837-43
pubmed: 9710453
PLoS One. 2013 Apr 08;8(4):e60028
pubmed: 23593160
J Cell Biol. 2015 Sep 14;210(6):1003-12
pubmed: 26347138
J Cell Mol Med. 2012 Dec;16(12):3105-15
pubmed: 22925160
Development. 2000 Nov;127(21):4531-40
pubmed: 11023857
Physiol Genomics. 2006 Feb 14;24(3):191-7
pubmed: 16352696
J Physiol Pharmacol. 2014 Apr;65(2):209-15
pubmed: 24781730
J Surg Res. 2006 Nov;136(1):85-91
pubmed: 16904693
FEBS Lett. 2005 Sep 12;579(22):5089-94
pubmed: 16137681
Trends Cardiovasc Med. 2007 May;17(4):140-3
pubmed: 17482097