Lactate metabolism coordinates macrophage response and regeneration in zebrafish
Macrophages are multifunctional cells with a pivotal role on tissue development, homeostasis and regeneration. Indeed, in response to tissue injury and the ensuing regeneration process, macrophages are challenged and undergo massive metabolic adaptations and changes. However, the control of this met...
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Veröffentlicht in: | Theranostics 2022-01, Vol.12 (8), p.3995-4009 |
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description | Macrophages are multifunctional cells with a pivotal role on tissue development, homeostasis and regeneration. Indeed, in response to tissue injury and the ensuing regeneration process, macrophages are challenged and undergo massive metabolic adaptations and changes. However, the control of this metabolic reprogramming by macrophage microenvironment has never been deciphered in vivo.
In this study, we used zebrafish model and caudal fin resection as a robust regeneration system. We explored specific changes in gene expression after tissue amputation via single-cell RNA sequencing analysis and whole-tissue transcriptomic analysis. Based on the identification of key modifications, we confirmed the role of the lactate pathway in macrophage response and fin regeneration, through the combination of chemical and genetic inhibitors of this pathway.
Single cell RNA sequencing revealed the upregulation of different genes associated with glycolysis and lactate metabolism in macrophages, upon fin regeneration. Hence, using chemical inhibitors of the LDH enzyme, we confirmed the role of lactate in macrophage recruitment and polarization, to promote a pro-inflammatory phenotype and enhance fin regeneration. The genetic modulation of monocarboxylate transporters illustrated a complex regulation of lactate levels, based on both intracellular and extracellular supplies. Commonly, the different sources of lactate resulted in macrophage activation with an increased expression level of inflammatory cytokines such as
during the first 24 hours of regeneration. Transcriptomic analyses confirmed that lactate induced a global modification of gene expression in macrophages.
Altogether, our findings highlight the crucial role of lactate at the onset of macrophage differentiation toward a pro-inflammatory phenotype. The deep modifications of macrophage phenotype mediated by lactate and downstream effectors play a key role to coordinate inflammatory response and tissue regeneration. |
doi_str_mv | 10.7150/THNO.65235 |
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In this study, we used zebrafish model and caudal fin resection as a robust regeneration system. We explored specific changes in gene expression after tissue amputation via single-cell RNA sequencing analysis and whole-tissue transcriptomic analysis. Based on the identification of key modifications, we confirmed the role of the lactate pathway in macrophage response and fin regeneration, through the combination of chemical and genetic inhibitors of this pathway.
Single cell RNA sequencing revealed the upregulation of different genes associated with glycolysis and lactate metabolism in macrophages, upon fin regeneration. Hence, using chemical inhibitors of the LDH enzyme, we confirmed the role of lactate in macrophage recruitment and polarization, to promote a pro-inflammatory phenotype and enhance fin regeneration. The genetic modulation of monocarboxylate transporters illustrated a complex regulation of lactate levels, based on both intracellular and extracellular supplies. Commonly, the different sources of lactate resulted in macrophage activation with an increased expression level of inflammatory cytokines such as
during the first 24 hours of regeneration. Transcriptomic analyses confirmed that lactate induced a global modification of gene expression in macrophages.
Altogether, our findings highlight the crucial role of lactate at the onset of macrophage differentiation toward a pro-inflammatory phenotype. The deep modifications of macrophage phenotype mediated by lactate and downstream effectors play a key role to coordinate inflammatory response and tissue regeneration.</description><identifier>ISSN: 1838-7640</identifier><identifier>EISSN: 1838-7640</identifier><identifier>DOI: 10.7150/THNO.65235</identifier><identifier>PMID: 35664055</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher Pty Ltd</publisher><subject>Amputation ; Embryos ; Experiments ; Gene expression ; Genetic engineering ; Laboratory animals ; Metabolism ; Microscopy ; Research Paper ; Veins & arteries ; Zebrafish</subject><ispartof>Theranostics, 2022-01, Vol.12 (8), p.3995-4009</ispartof><rights>The author(s).</rights><rights>2022. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The author(s) 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-ae42a927384cb5fdb6a56fa6e56c2fe61df14d157aa11a6b14e3725c4eb7cb763</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131269/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131269/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35664055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bohaud, Candice</creatorcontrib><creatorcontrib>Cruz, Jholy De La</creatorcontrib><creatorcontrib>Terraza, Claudia</creatorcontrib><creatorcontrib>Barthelaix, Audrey</creatorcontrib><creatorcontrib>Laplace-Builhé, Béryl</creatorcontrib><creatorcontrib>Jorgensen, Christian</creatorcontrib><creatorcontrib>Arribat, Yoan</creatorcontrib><creatorcontrib>Djouad, Farida</creatorcontrib><title>Lactate metabolism coordinates macrophage response and regeneration in zebrafish</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>Macrophages are multifunctional cells with a pivotal role on tissue development, homeostasis and regeneration. Indeed, in response to tissue injury and the ensuing regeneration process, macrophages are challenged and undergo massive metabolic adaptations and changes. However, the control of this metabolic reprogramming by macrophage microenvironment has never been deciphered in vivo.
In this study, we used zebrafish model and caudal fin resection as a robust regeneration system. We explored specific changes in gene expression after tissue amputation via single-cell RNA sequencing analysis and whole-tissue transcriptomic analysis. Based on the identification of key modifications, we confirmed the role of the lactate pathway in macrophage response and fin regeneration, through the combination of chemical and genetic inhibitors of this pathway.
Single cell RNA sequencing revealed the upregulation of different genes associated with glycolysis and lactate metabolism in macrophages, upon fin regeneration. Hence, using chemical inhibitors of the LDH enzyme, we confirmed the role of lactate in macrophage recruitment and polarization, to promote a pro-inflammatory phenotype and enhance fin regeneration. The genetic modulation of monocarboxylate transporters illustrated a complex regulation of lactate levels, based on both intracellular and extracellular supplies. Commonly, the different sources of lactate resulted in macrophage activation with an increased expression level of inflammatory cytokines such as
during the first 24 hours of regeneration. Transcriptomic analyses confirmed that lactate induced a global modification of gene expression in macrophages.
Altogether, our findings highlight the crucial role of lactate at the onset of macrophage differentiation toward a pro-inflammatory phenotype. The deep modifications of macrophage phenotype mediated by lactate and downstream effectors play a key role to coordinate inflammatory response and tissue regeneration.</description><subject>Amputation</subject><subject>Embryos</subject><subject>Experiments</subject><subject>Gene expression</subject><subject>Genetic engineering</subject><subject>Laboratory animals</subject><subject>Metabolism</subject><subject>Microscopy</subject><subject>Research Paper</subject><subject>Veins & arteries</subject><subject>Zebrafish</subject><issn>1838-7640</issn><issn>1838-7640</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdkUtLxTAQhYMoKurGHyAFNyJcTdI82o0g4gsu6kLXYZpO7420yTXpFfTXG5-os8lM5uNwkkPILqNHmkl6fH91c3ukJC_lCtlkVVlNtBJ09Ve_QXZSeqS5BOU1q9fJRilVXki5Se6mYEcYsRhwhCb0Lg2FDSG2zufbVAxgY1jMYYZFxLQIPmEBvs3DDD1GGF3whfPFKzYROpfm22Stgz7hzte5RR4uzu_PribT28vrs9PpxAqqxgmg4FBzXVbCNrJrGwVSdaBQKss7VKztmGiZ1ACMgWqYwFJzaQU22jZalVvk5FN3sWwGbC36MUJvFtENEF9MAGf-brybm1l4NjUrGVd1Fjj4EojhaYlpNINLFvsePIZlMlxpQWmla5nR_X_oY1hGn59nuFa0UrUQLFOHn1T-sZQidj9mGDXvWZlx7oP5yCrDe7_t_6DfyZRv_0aRNA</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Bohaud, Candice</creator><creator>Cruz, Jholy De La</creator><creator>Terraza, Claudia</creator><creator>Barthelaix, Audrey</creator><creator>Laplace-Builhé, Béryl</creator><creator>Jorgensen, Christian</creator><creator>Arribat, Yoan</creator><creator>Djouad, Farida</creator><general>Ivyspring International Publisher Pty Ltd</general><general>Ivyspring International Publisher</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220101</creationdate><title>Lactate metabolism coordinates macrophage response and regeneration in zebrafish</title><author>Bohaud, Candice ; Cruz, Jholy De La ; Terraza, Claudia ; Barthelaix, Audrey ; Laplace-Builhé, Béryl ; Jorgensen, Christian ; Arribat, Yoan ; Djouad, Farida</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-ae42a927384cb5fdb6a56fa6e56c2fe61df14d157aa11a6b14e3725c4eb7cb763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Amputation</topic><topic>Embryos</topic><topic>Experiments</topic><topic>Gene expression</topic><topic>Genetic engineering</topic><topic>Laboratory animals</topic><topic>Metabolism</topic><topic>Microscopy</topic><topic>Research Paper</topic><topic>Veins & arteries</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bohaud, Candice</creatorcontrib><creatorcontrib>Cruz, Jholy De La</creatorcontrib><creatorcontrib>Terraza, Claudia</creatorcontrib><creatorcontrib>Barthelaix, Audrey</creatorcontrib><creatorcontrib>Laplace-Builhé, Béryl</creatorcontrib><creatorcontrib>Jorgensen, Christian</creatorcontrib><creatorcontrib>Arribat, Yoan</creatorcontrib><creatorcontrib>Djouad, Farida</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Theranostics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bohaud, Candice</au><au>Cruz, Jholy De La</au><au>Terraza, Claudia</au><au>Barthelaix, Audrey</au><au>Laplace-Builhé, Béryl</au><au>Jorgensen, Christian</au><au>Arribat, Yoan</au><au>Djouad, Farida</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lactate metabolism coordinates macrophage response and regeneration in zebrafish</atitle><jtitle>Theranostics</jtitle><addtitle>Theranostics</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>12</volume><issue>8</issue><spage>3995</spage><epage>4009</epage><pages>3995-4009</pages><issn>1838-7640</issn><eissn>1838-7640</eissn><abstract>Macrophages are multifunctional cells with a pivotal role on tissue development, homeostasis and regeneration. Indeed, in response to tissue injury and the ensuing regeneration process, macrophages are challenged and undergo massive metabolic adaptations and changes. However, the control of this metabolic reprogramming by macrophage microenvironment has never been deciphered in vivo.
In this study, we used zebrafish model and caudal fin resection as a robust regeneration system. We explored specific changes in gene expression after tissue amputation via single-cell RNA sequencing analysis and whole-tissue transcriptomic analysis. Based on the identification of key modifications, we confirmed the role of the lactate pathway in macrophage response and fin regeneration, through the combination of chemical and genetic inhibitors of this pathway.
Single cell RNA sequencing revealed the upregulation of different genes associated with glycolysis and lactate metabolism in macrophages, upon fin regeneration. Hence, using chemical inhibitors of the LDH enzyme, we confirmed the role of lactate in macrophage recruitment and polarization, to promote a pro-inflammatory phenotype and enhance fin regeneration. The genetic modulation of monocarboxylate transporters illustrated a complex regulation of lactate levels, based on both intracellular and extracellular supplies. Commonly, the different sources of lactate resulted in macrophage activation with an increased expression level of inflammatory cytokines such as
during the first 24 hours of regeneration. Transcriptomic analyses confirmed that lactate induced a global modification of gene expression in macrophages.
Altogether, our findings highlight the crucial role of lactate at the onset of macrophage differentiation toward a pro-inflammatory phenotype. The deep modifications of macrophage phenotype mediated by lactate and downstream effectors play a key role to coordinate inflammatory response and tissue regeneration.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>35664055</pmid><doi>10.7150/THNO.65235</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amputation Embryos Experiments Gene expression Genetic engineering Laboratory animals Metabolism Microscopy Research Paper Veins & arteries Zebrafish |
title | Lactate metabolism coordinates macrophage response and regeneration in zebrafish |
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