MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation
G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand–receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/109190 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-5629-4798 |
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| author | Papangeli, Irinna Kim, Jongmin Maier, Inna Park, Saejeong Lee, Aram Kang, Yujung Tanaka, Keiichiro Ju, Hyekyung Kojima, Yoko Red-Horse, Kristy Siekmann, Arndt F. Chun, Hyung J. Khan, Omar Fizal Anderson, Daniel Griffith |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Papangeli, Irinna Kim, Jongmin Maier, Inna Park, Saejeong Lee, Aram Kang, Yujung Tanaka, Keiichiro Ju, Hyekyung Kojima, Yoko Red-Horse, Kristy Siekmann, Arndt F. Chun, Hyung J. Khan, Omar Fizal Anderson, Daniel Griffith |
| author_sort | Papangeli, Irinna |
| collection | MIT |
| description | G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand–receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice with Apln, Aplnr or endothelial-specific Aplnr deletion develop profound retinal vascular defects, which are at least in part due to dysregulated increase in endothelial CXCR4 expression. Endothelial CXCR4 is negatively regulated by miR-139-5p, whose transcription is in turn induced by laminar flow and APLN/APLNR signalling. Inhibition of miR-139-5p in vivo partially phenocopies the retinal vascular defects of APLN/APLNR deficiency. Pharmacological inhibition of CXCR4 signalling or augmentation of the miR-139-5p-CXCR4 axis can ameliorate the vascular phenotype of APLN/APLNR deficient state. Overall, we identify an important microRNA-mediated GPCR crosstalk, which plays a key role in vascular development. |
| first_indexed | 2024-09-23T13:29:45Z |
| format | Article |
| id | mit-1721.1/109190 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:29:45Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1091902022-09-28T14:36:09Z MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation Papangeli, Irinna Kim, Jongmin Maier, Inna Park, Saejeong Lee, Aram Kang, Yujung Tanaka, Keiichiro Ju, Hyekyung Kojima, Yoko Red-Horse, Kristy Siekmann, Arndt F. Chun, Hyung J. Khan, Omar Fizal Anderson, Daniel Griffith Harvard University--MIT Division of Health Sciences and Technology Koch Institute for Integrative Cancer Research at MIT Khan, Omar Fizal Anderson, Daniel Griffith G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand–receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice with Apln, Aplnr or endothelial-specific Aplnr deletion develop profound retinal vascular defects, which are at least in part due to dysregulated increase in endothelial CXCR4 expression. Endothelial CXCR4 is negatively regulated by miR-139-5p, whose transcription is in turn induced by laminar flow and APLN/APLNR signalling. Inhibition of miR-139-5p in vivo partially phenocopies the retinal vascular defects of APLN/APLNR deficiency. Pharmacological inhibition of CXCR4 signalling or augmentation of the miR-139-5p-CXCR4 axis can ameliorate the vascular phenotype of APLN/APLNR deficient state. Overall, we identify an important microRNA-mediated GPCR crosstalk, which plays a key role in vascular development. 2017-05-18T22:43:50Z 2017-05-18T22:43:50Z 2016-04 2015-04 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/109190 Papangeli, Irinna, Jongmin Kim, Inna Maier, Saejeong Park, Aram Lee, Yujung Kang, Keiichiro Tanaka, et al. “MicroRNA 139-5p Coordinates APLNR-CXCR4 Crosstalk During Vascular Maturation.” Nat Comms 7 (April 12, 2016): 11268. © 2017 Macmillan Publishers Limited https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-5629-4798 en_US http://dx.doi.org/10.1038/ncomms11268 Nature Communications Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Publishing Group |
| spellingShingle | Papangeli, Irinna Kim, Jongmin Maier, Inna Park, Saejeong Lee, Aram Kang, Yujung Tanaka, Keiichiro Ju, Hyekyung Kojima, Yoko Red-Horse, Kristy Siekmann, Arndt F. Chun, Hyung J. Khan, Omar Fizal Anderson, Daniel Griffith MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation |
| title | MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation |
| title_full | MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation |
| title_fullStr | MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation |
| title_full_unstemmed | MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation |
| title_short | MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation |
| title_sort | microrna 139 5p coordinates aplnr cxcr4 crosstalk during vascular maturation |
| url | http://hdl.handle.net/1721.1/109190 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-5629-4798 |
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