Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization.
MCT1
angiogenesis
angriocrine signals
endothelial cells
ischemia
lactate
macrophage polarization
metabolism
muscle regeneration
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
received:
12
12
2019
revised:
14
04
2020
accepted:
07
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
10
11
2021
Statut:
ppublish
Résumé
Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype. Mechanistically, loss of pfkfb3 reduced lactate secretion by ECs and lowered lactate levels in the ischemic muscle. Addition of lactate to pfkfb3-deficient ECs restored M2-like polarization in an MCT1-dependent fashion. Lactate shuttling by ECs enabled macrophages to promote proliferation and fusion of muscle progenitors. Moreover, VEGF production by lactate-polarized macrophages was increased, resulting in a positive feedback loop that further stimulated angiogenesis. Finally, increasing lactate levels during ischemia rescued macrophage polarization and improved muscle reperfusion and regeneration, whereas macrophage-specific mct1 deletion prevented M2-like polarization. In summary, ECs exploit glycolysis for angiocrine lactate shuttling to steer muscle regeneration from ischemia.
Identifiants
pubmed: 32492393
pii: S1550-4131(20)30243-6
doi: 10.1016/j.cmet.2020.05.004
pmc: PMC7267778
pii:
doi:
Substances chimiques
Lactates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1136-1153.e7Subventions
Organisme : European Research Council
ID : 771486
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Authors declare no competing interests.
Références
Cell Stem Cell. 2018 Oct 4;23(4):530-543.e9
pubmed: 30290177
J Clin Invest. 2004 Feb;113(4):516-27
pubmed: 14966561
Physiology (Bethesda). 2015 Nov;30(6):417-27
pubmed: 26525341
Nat Immunol. 2017 Sep;18(9):985-994
pubmed: 28714978
Cell Metab. 2016 Nov 8;24(5):701-715
pubmed: 27773694
J Appl Physiol (1985). 1986 Apr;60(4):1116-20
pubmed: 3084443
Genesis. 2008 Feb;46(2):74-80
pubmed: 18257043
Cell. 2011 Oct 28;147(3):539-53
pubmed: 22036563
Physiol Rev. 2013 Jan;93(1):23-67
pubmed: 23303905
Methods Mol Biol. 2019;1862:121-136
pubmed: 30315464
Arterioscler Thromb Vasc Biol. 2014 Jun;34(6):1231-9
pubmed: 24700124
J Immunol. 2012 Oct 1;189(7):3669-80
pubmed: 22933625
Nat Commun. 2020 Jan 10;11(1):174
pubmed: 31924757
Cell. 2011 Sep 16;146(6):873-87
pubmed: 21925313
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3287-92
pubmed: 19966309
J Mol Cell Cardiol. 1990 Dec;22(12):1393-404
pubmed: 2089157
Neuron. 2014 Aug 6;83(3):572-85
pubmed: 25043422
Cell. 2013 Aug 1;154(3):651-63
pubmed: 23911327
Nature. 2008 Dec 11;456(7223):814-8
pubmed: 18997773
Science. 2003 Feb 7;299(5608):890-3
pubmed: 12574630
Nature. 2019 Apr;568(7750):117-121
pubmed: 30814728
Immunobiology. 2014 Mar;219(3):172-8
pubmed: 24080029
J Leukoc Biol. 2002 Apr;71(4):597-602
pubmed: 11927645
Nature. 2014 Sep 25;513(7519):559-63
pubmed: 25043024
J Vis Exp. 2017 Apr 27;(122):
pubmed: 28518103
Nat Immunol. 2013 Oct;14(10):1045-53
pubmed: 23995233
Circulation. 2019 Jan 8;139(2):226-242
pubmed: 30586702
Angiogenesis. 2012 Dec;15(4):581-92
pubmed: 22660894
Immunity. 2013 Apr 18;38(4):633-43
pubmed: 23601682
Nat Protoc. 2009;4(12):1737-46
pubmed: 19893509
J Physiol. 2007 Jan 1;578(Pt 1):327-36
pubmed: 17038433
Front Immunol. 2019 Jul 03;10:1462
pubmed: 31333642
Nat Rev Immunol. 2008 Dec;8(12):958-69
pubmed: 19029990
Am J Pathol. 2015 Sep;185(9):2482-94
pubmed: 26193666
Front Physiol. 2016 Aug 29;7:372
pubmed: 27621709
Nature. 2017 May 11;545(7653):224-228
pubmed: 28467822
J Clin Invest. 2008 Dec;118(12):3930-42
pubmed: 19033663
Cancer Cell. 2013 Dec 9;24(6):695-709
pubmed: 24332039
Sci Rep. 2017 Mar 07;7:43935
pubmed: 28266625
Cell Metab. 2013 Aug 6;18(2):251-64
pubmed: 23931756
Stem Cells. 2013 Feb;31(2):384-96
pubmed: 23169615
Front Cell Dev Biol. 2018 Sep 11;6:100
pubmed: 30255018
Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):580-585
pubmed: 28049847
Acta Neuropathol. 1995;89(4):380-4
pubmed: 7610771
Genesis. 2007 Sep;45(9):593-605
pubmed: 17868096
Cancer Res. 2011 Apr 1;71(7):2550-60
pubmed: 21300765
Stem Cell Reports. 2017 Dec 12;9(6):2018-2033
pubmed: 29198825
EMBO Rep. 2013 Dec;14(12):1062-72
pubmed: 24232182
Annu Rev Physiol. 2017 Feb 10;79:43-66
pubmed: 27992732
Nat Cell Biol. 2014 Nov;16(11):1045-56
pubmed: 25283993
Trends Immunol. 2017 Jun;38(6):395-406
pubmed: 28396078
Mol Ther. 2004 Nov;10(5):844-54
pubmed: 15509502
Nat Chem Biol. 2005 Dec;1(7):371-6
pubmed: 16370372
Skelet Muscle. 2018 Aug 6;8(1):25
pubmed: 30081940
Nat Genet. 2008 Feb;40(2):170-80
pubmed: 18176562
Stem Cells Int. 2019 Jul 14;2019:4761427
pubmed: 31396285
Blood. 2012 Oct 11;120(15):3152-62
pubmed: 22919031
Angiogenesis. 2014 Jan;17(1):109-18
pubmed: 24013945
Nature. 2017 Nov 2;551(7678):115-118
pubmed: 29045397
Science. 2017 Aug 25;357(6353):
pubmed: 28775214
J Appl Physiol (1985). 1999 Nov;87(5):1684-96
pubmed: 10562610
J Neurosci. 2011 Jan 5;31(1):225-33
pubmed: 21209208
Transgenic Res. 1999 Aug;8(4):265-77
pubmed: 10621974
Am J Physiol. 1997 Jul;273(1 Pt 1):C205-13
pubmed: 9252458
Science. 2014 Jan 24;343(6169):416-9
pubmed: 24458641
Cell Metab. 2014 Jan 7;19(1):37-48
pubmed: 24332967
Nat Commun. 2017 Oct 16;8(1):952
pubmed: 29038527
Nature. 2010 Nov 11;468(7321):310-5
pubmed: 21068842
Cancer Cell. 2016 Dec 12;30(6):968-985
pubmed: 27866851
Cell Metab. 2018 Apr 3;27(4):757-785
pubmed: 29617642
Front Immunol. 2018 Feb 19;9:270
pubmed: 29520272
Med Sci Sports Exerc. 1986 Jun;18(3):360-8
pubmed: 3523107
J Exp Med. 2016 Jan 11;213(1):15-23
pubmed: 26694970
Nature. 2016 Jan 21;529(7586):316-25
pubmed: 26791722
J Immunol. 2016 Jun 1;196(11):4771-82
pubmed: 27183604
Nat Rev Mol Cell Biol. 2016 May;17(5):267-79
pubmed: 26956195
Nat Rev Mol Cell Biol. 2007 Jun;8(6):464-78
pubmed: 17522591
Nat Rev Immunol. 2017 Mar;17(3):165-178
pubmed: 28163303
J Exp Med. 2007 May 14;204(5):1057-69
pubmed: 17485518
Nat Med. 1999 Jun;5(6):623-8
pubmed: 10371499