The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization
Open accessAbstract
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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Gasdermin D-mediated metabolic crosstalk promotes tissue repair
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Metadata
- Authors
- Zhang, J., Muri, J., Fitzgerald, G., Gorski, T., Gianni-Barrera, R., Masschelein, E., D’Hulst, G., Gilardoni, P., Turiel, G., Fan, Z., Wang, T., Planque, M., Carmeliet, P., Pellerin, L., Wolfrum, C., Fendt, S.-M., Banfi, A., Stockmann, C., Soro-Arnáiz, I., Kopf, M., & De Bock, K.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 31
- Issue
- 6
- Pages
- 1136-1153.e7
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W3031352795
- Cited by
- 533
- References
- 79
- FWCI
- 14.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zhang, J., Muri, J., Fitzgerald, G., Gorski, T., Gianni-Barrera, R., Masschelein, E., D’Hulst, G., Gilardoni, P., Turiel, G., Fan, Z., Wang, T., Planque, M., Carmeliet, P., Pellerin, L., Wolfrum, C., Fendt, S.-M., Banfi, A., Stockmann, C., Soro-Arnáiz, I., . . . De Bock, K. (2020). Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization. Cell Metabolism. https://doi.org/10.1016/j.cmet.2020.05.004
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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