A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression
Abstract Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under‐explored. Human embryonic stem cell‐derived mesenchymal stem cells (hES‐MSCs) are shown to exert more potent cardioprotective effects against card...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202004629 |
| _version_ | 1818738287290875904 |
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| author | Rongrong Wu Wangxing Hu Huan Chen Yingchao Wang Qingju Li Changchen Xiao Lin Fan Zhiwei Zhong Xiaoying Chen Kaiqi Lv Shuhan Zhong Yanna Shi Jinghai Chen Wei Zhu Jianyi Zhang Xinyang Hu Jian'an Wang |
| author_facet | Rongrong Wu Wangxing Hu Huan Chen Yingchao Wang Qingju Li Changchen Xiao Lin Fan Zhiwei Zhong Xiaoying Chen Kaiqi Lv Shuhan Zhong Yanna Shi Jinghai Chen Wei Zhu Jianyi Zhang Xinyang Hu Jian'an Wang |
| author_sort | Rongrong Wu |
| collection | DOAJ |
| description | Abstract Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under‐explored. Human embryonic stem cell‐derived mesenchymal stem cells (hES‐MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow‐derived MSCs (hBM‐MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES‐MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES‐MSCs versus hBM‐MSCs, and named as SCDAL (stem cell‐derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES‐MSCs in the infarcted hearts, while overexpression of SCDAL in either hES‐MSCs or hBM‐MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non‐canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL‐GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA‐dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL‐GDF6 pathway has potential as a therapy for ischemic heart diseases. |
| first_indexed | 2024-12-18T01:06:32Z |
| format | Article |
| id | doaj.art-620cbd72b8f947d887887cb1ba30f197 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-18T01:06:32Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-620cbd72b8f947d887887cb1ba30f1972022-12-21T21:26:13ZengWileyAdvanced Science2198-38442021-09-01818n/an/a10.1002/advs.202004629A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 ExpressionRongrong Wu0Wangxing Hu1Huan Chen2Yingchao Wang3Qingju Li4Changchen Xiao5Lin Fan6Zhiwei Zhong7Xiaoying Chen8Kaiqi Lv9Shuhan Zhong10Yanna Shi11Jinghai Chen12Wei Zhu13Jianyi Zhang14Xinyang Hu15Jian'an Wang16Department of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaKey Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province Hangzhou 310012 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Biomedical Engineering University of Alabama at Birmingham School of Medicine and School of Engineering Birmingham AL 35294 USADepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaDepartment of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310009 P. R. ChinaAbstract Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under‐explored. Human embryonic stem cell‐derived mesenchymal stem cells (hES‐MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow‐derived MSCs (hBM‐MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES‐MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES‐MSCs versus hBM‐MSCs, and named as SCDAL (stem cell‐derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES‐MSCs in the infarcted hearts, while overexpression of SCDAL in either hES‐MSCs or hBM‐MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non‐canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL‐GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA‐dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL‐GDF6 pathway has potential as a therapy for ischemic heart diseases.https://doi.org/10.1002/advs.202004629angiogenesisgrowth differentiation factor 6myocardial infarctionSCDAL |
| spellingShingle | Rongrong Wu Wangxing Hu Huan Chen Yingchao Wang Qingju Li Changchen Xiao Lin Fan Zhiwei Zhong Xiaoying Chen Kaiqi Lv Shuhan Zhong Yanna Shi Jinghai Chen Wei Zhu Jianyi Zhang Xinyang Hu Jian'an Wang A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression Advanced Science angiogenesis growth differentiation factor 6 myocardial infarction SCDAL |
| title | A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression |
| title_full | A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression |
| title_fullStr | A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression |
| title_full_unstemmed | A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression |
| title_short | A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression |
| title_sort | novel human long noncoding rna scdal promotes angiogenesis through snf5 mediated gdf6 expression |
| topic | angiogenesis growth differentiation factor 6 myocardial infarction SCDAL |
| url | https://doi.org/10.1002/advs.202004629 |
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