PMID- 27792641
OWN - NLM
STAT- MEDLINE
DCOM- 20171219
LR  - 20181113
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 5
IP  - 10
DP  - 2016 Oct 6
TI  - LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue 
      Regeneration.
LID - e004117
AB  - 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-beta (TGF-beta) expression, whereas supplementation of exogenous TGF-beta 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.
CI  - (c) 2016 The Authors. Published on behalf of the American Heart Association, Inc., 
      by Wiley Blackwell.
FAU - Meng, Shu
AU  - Meng S
AD  - Center for Cardiovascular Regeneration, Houston Methodist Research Institute, 
      Houston, TX.
FAU - Matrone, Gianfranco
AU  - Matrone G
AD  - Center for Cardiovascular Regeneration, Houston Methodist Research Institute, 
      Houston, TX.
FAU - Lv, Jie
AU  - Lv J
AD  - Center for Cardiovascular Regeneration, Houston Methodist Research Institute, 
      Houston, TX.
FAU - Chen, Kaifu
AU  - Chen K
AD  - Center for Cardiovascular Regeneration, Houston Methodist Research Institute, 
      Houston, TX.
FAU - Wong, Wing Tak
AU  - Wong WT
AD  - Center for Cardiovascular Regeneration, Houston Methodist Research Institute, 
      Houston, TX.
FAU - Cooke, John P
AU  - Cooke JP
AD  - Center for Cardiovascular Regeneration, Houston Methodist Research Institute, 
      Houston, TX jpcooke@houstonmethodist.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161006
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (LIM Domain Proteins)
RN  - 0 (LMO2 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (lmo2 protein, zebrafish)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Animal Fins
MH  - Animals
MH  - Cell Proliferation/*genetics
MH  - *Endothelial Cells
MH  - Flow Cytometry
MH  - Gene Knockdown Techniques
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - LIM Domain Proteins/*genetics
MH  - Neovascularization, Physiologic/*genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Regeneration/*genetics
MH  - Transcription Factors/*genetics
MH  - Zebrafish
MH  - Zebrafish Proteins/*genetics
PMC - PMC5121509
OTO - NOTNLM
OT  - LIM domain only 2
OT  - angiogenesis
OT  - endothelial cell
OT  - proliferation
OT  - regeneration
OT  - transcription factors
EDAT- 2016/10/30 06:00
MHDA- 2017/12/20 06:00
PMCR- 2016/10/01
CRDT- 2016/10/30 06:00
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/12/20 06:00 [medline]
PHST- 2016/10/30 06:00 [entrez]
PHST- 2016/10/01 00:00 [pmc-release]
AID - JAHA.116.004117 [pii]
AID - JAH31811 [pii]
AID - 10.1161/JAHA.116.004117 [doi]
PST - epublish
SO  - J Am Heart Assoc. 2016 Oct 6;5(10):e004117. doi: 10.1161/JAHA.116.004117.