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Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis
Indoleamine 2,3 dioxygenase-1 (IDO1) catalyzes tryptophan-kynurenine metabolism in many inflammatory and cancer diseases. Of note, acute inflammation that occurs immediately after heart injury is essential for neonatal cardiomyocyte proliferation and heart regeneration. However, the IDO1-catalyzed t...
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| Published in: | Nature communications 2022-10, Vol.13 (1), p.6371-6371, Article 6371 |
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| container_title | Nature communications |
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| creator | Zhang, Donghong Ning, Jinfeng Ramprasath, Tharmarajan Yu, Changjiang Zheng, Xiaoxu Song, Ping Xie, Zhonglin Zou, Ming-Hui |
| description | Indoleamine 2,3 dioxygenase-1 (IDO1) catalyzes tryptophan-kynurenine metabolism in many inflammatory and cancer diseases. Of note, acute inflammation that occurs immediately after heart injury is essential for neonatal cardiomyocyte proliferation and heart regeneration. However, the IDO1-catalyzed tryptophan metabolism during heart regeneration is largely unexplored. Here, we find that apical neonatal mouse heart resection surgery led to rapid and consistent increases in cardiac IDO1 expression and kynurenine accumulation. Cardiac deletion of
Ido1
gene or chemical inhibition of IDO1 impairs heart regeneration. Mechanistically, elevated kynurenine triggers cardiomyocyte proliferation by activating the cytoplasmic aryl hydrocarbon receptor-SRC-YAP/ERK pathway. In addition, cardiomyocyte-derived kynurenine transports to endothelial cells and stimulates cardiac angiogenesis by promoting aryl hydrocarbon receptor nuclear translocation and enhancing vascular endothelial growth factor A expression. Notably,
Ahr
deletion prevents indoleamine 2,3 dioxygenase -kynurenine–associated heart regeneration. In summary, increasing indoleamine 2,3 dioxygenase-derived kynurenine level promotes cardiac regeneration by functioning as an endogenous regulator of cardiomyocyte proliferation and cardiac angiogenesis.
Failed cardiac regeneration to repair adult acute myocardial ischemia is the leading cause of heart failure. Here, the authors show that IDO1-derived kynurenine metabolism promotes cardiomyocyte proliferation and cardiac angiogenesis via cytoplasmic aryl hydrocarbon receptor (AhR) and nucleic AhR translocation signalling. |
| doi_str_mv | 10.1038/s41467-022-33734-7 |
| format | article |
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Ido1
gene or chemical inhibition of IDO1 impairs heart regeneration. Mechanistically, elevated kynurenine triggers cardiomyocyte proliferation by activating the cytoplasmic aryl hydrocarbon receptor-SRC-YAP/ERK pathway. In addition, cardiomyocyte-derived kynurenine transports to endothelial cells and stimulates cardiac angiogenesis by promoting aryl hydrocarbon receptor nuclear translocation and enhancing vascular endothelial growth factor A expression. Notably,
Ahr
deletion prevents indoleamine 2,3 dioxygenase -kynurenine–associated heart regeneration. In summary, increasing indoleamine 2,3 dioxygenase-derived kynurenine level promotes cardiac regeneration by functioning as an endogenous regulator of cardiomyocyte proliferation and cardiac angiogenesis.
Failed cardiac regeneration to repair adult acute myocardial ischemia is the leading cause of heart failure. Here, the authors show that IDO1-derived kynurenine metabolism promotes cardiomyocyte proliferation and cardiac angiogenesis via cytoplasmic aryl hydrocarbon receptor (AhR) and nucleic AhR translocation signalling.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/s41467-022-33734-7</identifier><identifier>PMID: 36289221</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/256 ; 692/4019/592/2725 ; 692/4019/592/75/230 ; 96 ; 96/1 ; 96/95 ; Angiogenesis ; Animals ; Aromatic compounds ; Cardiomyocytes ; Cell Proliferation ; Congestive heart failure ; Dioxygenase ; Endothelial cells ; Endothelial Cells - metabolism ; Gene deletion ; Growth factors ; Heart ; Humanities and Social Sciences ; Hydrocarbons ; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism ; Ischemia ; Kynurenine - metabolism ; Metabolic pathways ; Metabolism ; Mice ; multidisciplinary ; Myocardial ischemia ; Myocytes, Cardiac - metabolism ; Neonates ; Nuclear transport ; Receptors ; Receptors, Aryl Hydrocarbon - genetics ; Receptors, Aryl Hydrocarbon - metabolism ; Regeneration ; Science ; Science (multidisciplinary) ; Signal transduction ; Signal Transduction - physiology ; Translocation ; Tryptophan ; Tryptophan - metabolism ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Yes-associated protein</subject><ispartof>Nature communications, 2022-10, Vol.13 (1), p.6371-6371, Article 6371</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-2ce9da90dfaee40aec6a61c046563d94fbc2f9f4a8f0de6ffbe3032b18f306163</citedby><cites>FETCH-LOGICAL-c540t-2ce9da90dfaee40aec6a61c046563d94fbc2f9f4a8f0de6ffbe3032b18f306163</cites><orcidid>0000-0001-6143-7204 ; 0000-0002-3913-0617 ; 0000-0002-6143-4270 ; 0000-0002-2115-5875</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2728828066/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2728828066?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,74998</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36289221$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Donghong</creatorcontrib><creatorcontrib>Ning, Jinfeng</creatorcontrib><creatorcontrib>Ramprasath, Tharmarajan</creatorcontrib><creatorcontrib>Yu, Changjiang</creatorcontrib><creatorcontrib>Zheng, Xiaoxu</creatorcontrib><creatorcontrib>Song, Ping</creatorcontrib><creatorcontrib>Xie, Zhonglin</creatorcontrib><creatorcontrib>Zou, Ming-Hui</creatorcontrib><title>Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Indoleamine 2,3 dioxygenase-1 (IDO1) catalyzes tryptophan-kynurenine metabolism in many inflammatory and cancer diseases. Of note, acute inflammation that occurs immediately after heart injury is essential for neonatal cardiomyocyte proliferation and heart regeneration. However, the IDO1-catalyzed tryptophan metabolism during heart regeneration is largely unexplored. Here, we find that apical neonatal mouse heart resection surgery led to rapid and consistent increases in cardiac IDO1 expression and kynurenine accumulation. Cardiac deletion of
Ido1
gene or chemical inhibition of IDO1 impairs heart regeneration. Mechanistically, elevated kynurenine triggers cardiomyocyte proliferation by activating the cytoplasmic aryl hydrocarbon receptor-SRC-YAP/ERK pathway. In addition, cardiomyocyte-derived kynurenine transports to endothelial cells and stimulates cardiac angiogenesis by promoting aryl hydrocarbon receptor nuclear translocation and enhancing vascular endothelial growth factor A expression. Notably,
Ahr
deletion prevents indoleamine 2,3 dioxygenase -kynurenine–associated heart regeneration. In summary, increasing indoleamine 2,3 dioxygenase-derived kynurenine level promotes cardiac regeneration by functioning as an endogenous regulator of cardiomyocyte proliferation and cardiac angiogenesis.
Failed cardiac regeneration to repair adult acute myocardial ischemia is the leading cause of heart failure. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Donghong</au><au>Ning, Jinfeng</au><au>Ramprasath, Tharmarajan</au><au>Yu, Changjiang</au><au>Zheng, Xiaoxu</au><au>Song, Ping</au><au>Xie, Zhonglin</au><au>Zou, Ming-Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2022-10-26</date><risdate>2022</risdate><volume>13</volume><issue>1</issue><spage>6371</spage><epage>6371</epage><pages>6371-6371</pages><artnum>6371</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Indoleamine 2,3 dioxygenase-1 (IDO1) catalyzes tryptophan-kynurenine metabolism in many inflammatory and cancer diseases. Of note, acute inflammation that occurs immediately after heart injury is essential for neonatal cardiomyocyte proliferation and heart regeneration. However, the IDO1-catalyzed tryptophan metabolism during heart regeneration is largely unexplored. Here, we find that apical neonatal mouse heart resection surgery led to rapid and consistent increases in cardiac IDO1 expression and kynurenine accumulation. Cardiac deletion of
Ido1
gene or chemical inhibition of IDO1 impairs heart regeneration. Mechanistically, elevated kynurenine triggers cardiomyocyte proliferation by activating the cytoplasmic aryl hydrocarbon receptor-SRC-YAP/ERK pathway. In addition, cardiomyocyte-derived kynurenine transports to endothelial cells and stimulates cardiac angiogenesis by promoting aryl hydrocarbon receptor nuclear translocation and enhancing vascular endothelial growth factor A expression. Notably,
Ahr
deletion prevents indoleamine 2,3 dioxygenase -kynurenine–associated heart regeneration. In summary, increasing indoleamine 2,3 dioxygenase-derived kynurenine level promotes cardiac regeneration by functioning as an endogenous regulator of cardiomyocyte proliferation and cardiac angiogenesis.
Failed cardiac regeneration to repair adult acute myocardial ischemia is the leading cause of heart failure. Here, the authors show that IDO1-derived kynurenine metabolism promotes cardiomyocyte proliferation and cardiac angiogenesis via cytoplasmic aryl hydrocarbon receptor (AhR) and nucleic AhR translocation signalling.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36289221</pmid><doi>10.1038/s41467-022-33734-7</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-6143-7204</orcidid><orcidid>https://orcid.org/0000-0002-3913-0617</orcidid><orcidid>https://orcid.org/0000-0002-6143-4270</orcidid><orcidid>https://orcid.org/0000-0002-2115-5875</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 2041-1723 |
| ispartof | Nature communications, 2022-10, Vol.13 (1), p.6371-6371, Article 6371 |
| issn | 2041-1723 2041-1723 |
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| source | Open Access: PubMed Central; Publicly Available Content Database; Nature; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 631/250/256 692/4019/592/2725 692/4019/592/75/230 96 96/1 96/95 Angiogenesis Animals Aromatic compounds Cardiomyocytes Cell Proliferation Congestive heart failure Dioxygenase Endothelial cells Endothelial Cells - metabolism Gene deletion Growth factors Heart Humanities and Social Sciences Hydrocarbons Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Ischemia Kynurenine - metabolism Metabolic pathways Metabolism Mice multidisciplinary Myocardial ischemia Myocytes, Cardiac - metabolism Neonates Nuclear transport Receptors Receptors, Aryl Hydrocarbon - genetics Receptors, Aryl Hydrocarbon - metabolism Regeneration Science Science (multidisciplinary) Signal transduction Signal Transduction - physiology Translocation Tryptophan Tryptophan - metabolism Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Yes-associated protein |
| title | Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T16%3A41%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Kynurenine%20promotes%20neonatal%20heart%20regeneration%20by%20stimulating%20cardiomyocyte%20proliferation%20and%20cardiac%20angiogenesis&rft.jtitle=Nature%20communications&rft.au=Zhang,%20Donghong&rft.date=2022-10-26&rft.volume=13&rft.issue=1&rft.spage=6371&rft.epage=6371&rft.pages=6371-6371&rft.artnum=6371&rft.issn=2041-1723&rft.eissn=2041-1723&rft_id=info:doi/10.1038/s41467-022-33734-7&rft_dat=%3Cproquest_doaj_%3E2729521196%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c540t-2ce9da90dfaee40aec6a61c046563d94fbc2f9f4a8f0de6ffbe3032b18f306163%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2728828066&rft_id=info:pmid/36289221&rfr_iscdi=true |