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LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration

BACKGROUND: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized. METHODS AND RESULTS: In vitro loss‐ and gain‐of‐function studies on LMO2 were per...

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Autores principales: Meng, Shu, Matrone, Gianfranco, Lv, Jie, Chen, Kaifu, Wong, Wing Tak, Cooke, John P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121509/
https://www.ncbi.nlm.nih.gov/pubmed/27792641
http://dx.doi.org/10.1161/JAHA.116.004117
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author Meng, Shu
Matrone, Gianfranco
Lv, Jie
Chen, Kaifu
Wong, Wing Tak
Cooke, John P.
author_facet Meng, Shu
Matrone, Gianfranco
Lv, Jie
Chen, Kaifu
Wong, Wing Tak
Cooke, John P.
author_sort Meng, Shu
collection PubMed
description BACKGROUND: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized. METHODS AND RESULTS: In vitro loss‐ and gain‐of‐function studies on LMO2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (KD) of LMO2, respectively. LMO2 KD significantly impaired endothelial proliferation. LMO2 controls endothelial G1/S transition through transcriptional regulation of cyclin‐dependent kinase 2 and 4 as determined by reverse transcription polymerase chain reaction (PCR), western blot, and chromatin immunoprecipitation, and also influences the expression of Cyclin D1 and Cyclin A1. LMO2 KD also impaired angiogenesis by reducing transforming growth factor‐β (TGF‐β) expression, whereas supplementation of exogenous TGF‐β restored defective network formation in LMO2 KD human umbilical vein endothelial cells. In a zebrafish model of caudal fin regeneration, RT‐PCR revealed that the lmo2 (zebrafish gene) gene was upregulated at day 5 postresection. The KD of lmo2 by vivo‐morpholino injections in adult Tg(fli1:egfp) (y1) zebrafish reduced 5‐bromo‐2′‐deoxyuridine incorporation in endothelial cells, impaired neoangiogenesis in the resected caudal fin, and substantially delayed fin regeneration. CONCLUSIONS: The transcriptional factor LMO2 regulates endothelial proliferation and angiogenesis in vitro. Furthermore, LMO2 is required for angiogenesis and tissue healing in vivo. Thus, LMO2 is a critical determinant of vascular and tissue regeneration.
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spelling pubmed-51215092016-12-06 LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration Meng, Shu Matrone, Gianfranco Lv, Jie Chen, Kaifu Wong, Wing Tak Cooke, John P. J Am Heart Assoc Original Research BACKGROUND: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized. METHODS AND RESULTS: In vitro loss‐ and gain‐of‐function studies on LMO2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (KD) of LMO2, respectively. LMO2 KD significantly impaired endothelial proliferation. LMO2 controls endothelial G1/S transition through transcriptional regulation of cyclin‐dependent kinase 2 and 4 as determined by reverse transcription polymerase chain reaction (PCR), western blot, and chromatin immunoprecipitation, and also influences the expression of Cyclin D1 and Cyclin A1. LMO2 KD also impaired angiogenesis by reducing transforming growth factor‐β (TGF‐β) expression, whereas supplementation of exogenous TGF‐β restored defective network formation in LMO2 KD human umbilical vein endothelial cells. In a zebrafish model of caudal fin regeneration, RT‐PCR revealed that the lmo2 (zebrafish gene) gene was upregulated at day 5 postresection. The KD of lmo2 by vivo‐morpholino injections in adult Tg(fli1:egfp) (y1) zebrafish reduced 5‐bromo‐2′‐deoxyuridine incorporation in endothelial cells, impaired neoangiogenesis in the resected caudal fin, and substantially delayed fin regeneration. CONCLUSIONS: The transcriptional factor LMO2 regulates endothelial proliferation and angiogenesis in vitro. Furthermore, LMO2 is required for angiogenesis and tissue healing in vivo. Thus, LMO2 is a critical determinant of vascular and tissue regeneration. John Wiley and Sons Inc. 2016-10-06 /pmc/articles/PMC5121509/ /pubmed/27792641 http://dx.doi.org/10.1161/JAHA.116.004117 Text en © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Meng, Shu
Matrone, Gianfranco
Lv, Jie
Chen, Kaifu
Wong, Wing Tak
Cooke, John P.
LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
title LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
title_full LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
title_fullStr LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
title_full_unstemmed LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
title_short LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
title_sort lim domain only 2 regulates endothelial proliferation, angiogenesis, and tissue regeneration
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121509/
https://www.ncbi.nlm.nih.gov/pubmed/27792641
http://dx.doi.org/10.1161/JAHA.116.004117
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