Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization
dc.contributor.author
Zhang, Jing
dc.contributor.author
Muri, Jonathan
dc.contributor.author
Fitzgerald, Gillian
dc.contributor.author
Gorski, Tatiane
dc.contributor.author
Gianni-Barrera, Roberto
dc.contributor.author
Masschelein, Evi
dc.contributor.author
D'Hulst, Gommaar
dc.contributor.author
Gilardoni, Paola
dc.contributor.author
Turiel, Guillermo
dc.contributor.author
Fan, Zheng
dc.contributor.author
Wang, TongTong
dc.contributor.author
Planque, Mélanie
dc.contributor.author
Carmeliet, Peter
dc.contributor.author
Pellerin, Luc
dc.contributor.author
Wolfrum, Christian
dc.contributor.author
Fendt, Sarah-Maria
dc.contributor.author
Banfi, Andrea
dc.contributor.author
Stockmann, Christian
dc.contributor.author
Soro-Arnaiz, Inés
dc.contributor.author
Kopf, Manfred
dc.contributor.author
De Bock, Katrien
dc.date.accessioned
2020-06-17T05:12:28Z
dc.date.available
2020-06-02T02:37:57Z
dc.date.available
2020-06-03T07:00:07Z
dc.date.available
2020-06-17T05:12:28Z
dc.date.issued
2020
dc.identifier.issn
1550-4131
dc.identifier.issn
1932-7420
dc.identifier.other
10.1016/j.cmet.2020.05.004
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/417556
dc.identifier.doi
10.3929/ethz-b-000417556
dc.description.abstract
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.
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application/pdf
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dc.language.iso
en
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dc.publisher
Cell Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title
Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2020-06-02
ethz.journal.title
Cell Metabolism
ethz.journal.volume
31
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ethz.journal.issue
6
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ethz.journal.abbreviated
Cell Metab
ethz.pages.start
1136
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1153.e7
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publishedVersion
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ethz.grant
Understanding Exercise-Induced Endothelial Metabolic Reprogramming To Promote Ischemic Revascularization
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ethz.grant
Identification of PPARg target genes in macrophages and characterization of their functional roles
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ethz.grant
Understanding the metabolic cross-talk between the muscle and the endothelium: implications for exercise training and insulin sensitivity
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Cambridge, MA
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published
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ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::09560 - De Bock, Katrien / De Bock, Katrien
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03596 - Kopf, Manfred / Kopf, Manfred
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
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ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
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ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::09560 - De Bock, Katrien / De Bock, Katrien
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03596 - Kopf, Manfred / Kopf, Manfred
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
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176056
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182829
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10.13039/501100000780
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H2020
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Projekte Lebenswissenschaften
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Exzellenzbeitrag in Lebenswissenschaften
ethz.date.deposited
2020-06-02T02:38:01Z
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SCOPUS
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Open access
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