<i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart Regeneration
The heart switches its main metabolic substrate from glucose to fatty acids shortly after birth, which is one of reasons for the loss of heart regeneration capability in adult mammals. On the contrary, metabolic shifts from oxidative phosphorylation to glucose metabolism promote cardiomyocyte (CM) p...
| 主要な著者: | , , , |
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| フォーマット: | 論文 |
| 言語: | English |
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MDPI AG
2023-06-01
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| シリーズ: | Journal of Cardiovascular Development and Disease |
| 主題: | |
| オンライン･アクセス: | https://www.mdpi.com/2308-3425/10/6/246 |
| _version_ | 1827736989399515136 |
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| author | Zimu Tang Kaiyuan Wang Lijian Lo Jun Chen |
| author_facet | Zimu Tang Kaiyuan Wang Lijian Lo Jun Chen |
| author_sort | Zimu Tang |
| collection | DOAJ |
| description | The heart switches its main metabolic substrate from glucose to fatty acids shortly after birth, which is one of reasons for the loss of heart regeneration capability in adult mammals. On the contrary, metabolic shifts from oxidative phosphorylation to glucose metabolism promote cardiomyocyte (CM) proliferation after heart injury. However, how glucose transportation in CMs is regulated during heart regeneration is still not fully understood. In this report, we found that the expression of Glut1 (<i>slc2a1</i>) was upregulated around the injury site of zebrafish heart, accompanied by an increase in glucose uptake at the injury area. Knockout of <i>slc2a1a</i> impaired zebrafish heart regeneration. Our previous study has demonstrated that the expression of <i>Δ113p53</i> is activated after heart injury and <i>Δ113p53</i><sup>+</sup> CMs undergo proliferation to contribute to zebrafish heart regeneration. Next, we used the <i>Δ113p53</i> promoter to generate the <i>Tg(Δ113p53:cmyc)</i> zebrafish transgenic line. Conditional overexpression of <i>cmyc</i> not only significantly promoted zebrafish CM proliferation and heart regeneration but also significantly enhanced <i>glut1</i> expression at the injury site. Inhibiting Glut1 diminished the increase in CM proliferation in <i>Tg(Δ113p53:cmyc)</i> injured hearts of zebrafish. Therefore, our results suggest that the activation of <i>cmyc</i> promotes heart regeneration through upregulating the expression of <i>glut1</i> to speed up glucose transportation. |
| first_indexed | 2024-03-11T02:19:50Z |
| format | Article |
| id | doaj.art-df34634cdaf5400bae271e6d3dba4bc8 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-11T02:19:50Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-df34634cdaf5400bae271e6d3dba4bc82023-11-18T10:57:30ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252023-06-0110624610.3390/jcdd10060246<i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart RegenerationZimu Tang0Kaiyuan Wang1Lijian Lo2Jun Chen3MOE Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Cancer Center, Zhejiang University, Hangzhou 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Cancer Center, Zhejiang University, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaMOE Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Cancer Center, Zhejiang University, Hangzhou 310058, ChinaThe heart switches its main metabolic substrate from glucose to fatty acids shortly after birth, which is one of reasons for the loss of heart regeneration capability in adult mammals. On the contrary, metabolic shifts from oxidative phosphorylation to glucose metabolism promote cardiomyocyte (CM) proliferation after heart injury. However, how glucose transportation in CMs is regulated during heart regeneration is still not fully understood. In this report, we found that the expression of Glut1 (<i>slc2a1</i>) was upregulated around the injury site of zebrafish heart, accompanied by an increase in glucose uptake at the injury area. Knockout of <i>slc2a1a</i> impaired zebrafish heart regeneration. Our previous study has demonstrated that the expression of <i>Δ113p53</i> is activated after heart injury and <i>Δ113p53</i><sup>+</sup> CMs undergo proliferation to contribute to zebrafish heart regeneration. Next, we used the <i>Δ113p53</i> promoter to generate the <i>Tg(Δ113p53:cmyc)</i> zebrafish transgenic line. Conditional overexpression of <i>cmyc</i> not only significantly promoted zebrafish CM proliferation and heart regeneration but also significantly enhanced <i>glut1</i> expression at the injury site. Inhibiting Glut1 diminished the increase in CM proliferation in <i>Tg(Δ113p53:cmyc)</i> injured hearts of zebrafish. Therefore, our results suggest that the activation of <i>cmyc</i> promotes heart regeneration through upregulating the expression of <i>glut1</i> to speed up glucose transportation.https://www.mdpi.com/2308-3425/10/6/246heart regenerationglut1cmyczebrafishglucose transportationcardiomyocyte proliferation |
| spellingShingle | Zimu Tang Kaiyuan Wang Lijian Lo Jun Chen <i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart Regeneration Journal of Cardiovascular Development and Disease heart regeneration glut1 cmyc zebrafish glucose transportation cardiomyocyte proliferation |
| title | <i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart Regeneration |
| title_full | <i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart Regeneration |
| title_fullStr | <i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart Regeneration |
| title_full_unstemmed | <i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart Regeneration |
| title_short | <i>Tg(Δ113p53:cmyc)</i> Transgene Upregulates <i>glut1</i> Expression to Promote Zebrafish Heart Regeneration |
| title_sort | i tg δ113p53 cmyc i transgene upregulates i glut1 i expression to promote zebrafish heart regeneration |
| topic | heart regeneration glut1 cmyc zebrafish glucose transportation cardiomyocyte proliferation |
| url | https://www.mdpi.com/2308-3425/10/6/246 |
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