PUBLICATION
LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
- Authors
- Meng, S., Matrone, G., Lv, J., Chen, K., Wong, W.T., Cooke, J.P.
- ID
- ZDB-PUB-161030-9
- Date
- 2016
- Source
- Journal of the American Heart Association 5(10): (Journal)
- Registered Authors
- Keywords
- LIM domain only 2, angiogenesis, endothelial cell, proliferation, regeneration, transcription factors
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/genetics*
- Animal Fins
- Animals
- Cell Proliferation/genetics*
- Endothelial Cells*
- Flow Cytometry
- Gene Knockdown Techniques
- Human Umbilical Vein Endothelial Cells
- Humans
- LIM Domain Proteins/genetics*
- Neovascularization, Physiologic/genetics*
- Proto-Oncogene Proteins/genetics*
- Real-Time Polymerase Chain Reaction
- Regeneration/genetics*
- Transcription Factors/genetics*
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 27792641 Full text @ J. Am. Heart Assoc.
Citation
Meng, S., Matrone, G., Lv, J., Chen, K., Wong, W.T., Cooke, J.P. (2016) LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration. Journal of the American Heart Association. 5(10).
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping