PMID- 31618597
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20220623
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 12
DP  - 2019 Dec
TI  - Prep1 regulates angiogenesis through a PGC-1alpha-mediated mechanism.
PG  - 13893-13904
LID - 10.1096/fj.201901230RR [doi]
AB  - Angiogenesis depends on a delicate balance between the different transcription 
      factors, and their control should be considered necessary for preventing or 
      treating diseases. Pre-B-cell leukemia transcription factor regulating protein 1 
      (Prep1) is a homeodomain transcription factor that plays a primary role in 
      organogenesis and metabolism. Observations performed in a Prep1 hypomorphic mouse 
      model, expressing 3-5% of the protein, show an increase of embryonic lethality 
      due, in part, to defects in angiogenesis. In this study, we provide evidence that 
      overexpression of Prep1 in mouse aortic endothelial cells (MAECs) stimulates 
      migration, proliferation, and tube formation. These effects are paralleled by an 
      increase of several proangiogenic factors and by a decrease of the antiangiogenic 
      gene neurogenic locus notch homolog protein 1 (Notch1). Prep1-mediated 
      angiogenesis involves the activation of the p160 Myb-binding protein 
      (p160)/peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) 
      pathway. Indeed, Prep1 overexpression increases its binding with p160 and induces 
      a 4-fold increase of p160 and 70% reduction of PGC-1alpha compared with control 
      cells. Incubation of MAECs with a synthetic Prep1(54-72) peptide, mimicking the 
      Prep1 region involved in the interaction with p160, reverts the proangiogenic 
      effects mediated by Prep1. In addition, Prep1 levels increase by 3.2-fold during 
      the fibroblast growth factor beta (bFGF)-mediated endothelial colony-forming cells' 
      activation, whereas Prep1(54-72) peptide reduces the capability of these cells to 
      generate tubular-like structures in response to bFGF, suggesting a possible role 
      of Prep1 both in angiogenesis from preexisting vessels and in postnatal 
      vasculogenesis. Finally, Prep1 hypomorphic heterozygous mice, expressing low 
      levels of Prep1, show attenuated placental angiogenesis and vessel formation 
      within Matrigel plugs. All of these observations indicate that Prep1, complexing 
      with p160, decreases PGC-1alpha and stimulates angiogenesis.-Cimmino, I., Margheri, 
      F., Prisco, F., Perruolo, G., D'Esposito, V., Laurenzana, A., Fibbi, G., 
      Paciello, O., Doti, N., Ruvo, M., Miele, C., Beguinot, F., Formisano, P., 
      Oriente, F. Prep1 regulates angiogenesis through a PGC-1alpha-mediated mechanism.
FAU - Cimmino, Ilaria
AU  - Cimmino I
AD  - Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, 
      Institute of Experimental Endocrinology and Oncology, National Council of 
      Research (CNR), University of Naples Federico II, Naples, Italy.
FAU - Margheri, Francesca
AU  - Margheri F
AD  - Department of Experimental and Clinical Biomedical Sciences Mario Serio, 
      University of Florence, Florence, Italy.
FAU - Prisco, Francesco
AU  - Prisco F
AD  - Department of Veterinary Medicine and Animal Production, University of Naples 
      Federico II, Naples, Italy.
FAU - Perruolo, Giuseppe
AU  - Perruolo G
AD  - Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, 
      Institute of Experimental Endocrinology and Oncology, National Council of 
      Research (CNR), University of Naples Federico II, Naples, Italy.
FAU - D'Esposito, Vittoria
AU  - D'Esposito V
AD  - Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, 
      Institute of Experimental Endocrinology and Oncology, National Council of 
      Research (CNR), University of Naples Federico II, Naples, Italy.
FAU - Laurenzana, Anna
AU  - Laurenzana A
AD  - Department of Experimental and Clinical Biomedical Sciences Mario Serio, 
      University of Florence, Florence, Italy.
FAU - Fibbi, Gabriella
AU  - Fibbi G
AD  - Department of Experimental and Clinical Biomedical Sciences Mario Serio, 
      University of Florence, Florence, Italy.
FAU - Paciello, Orlando
AU  - Paciello O
AD  - Department of Veterinary Medicine and Animal Production, University of Naples 
      Federico II, Naples, Italy.
FAU - Doti, Nunzianna
AU  - Doti N
AD  - Institute of Biostructure and Bioimaging, National Research 
      Council-Interuniversity Research Centre on Bioactive Peptides, Naples, Italy.
FAU - Ruvo, Menotti
AU  - Ruvo M
AD  - Institute of Biostructure and Bioimaging, National Research 
      Council-Interuniversity Research Centre on Bioactive Peptides, Naples, Italy.
FAU - Miele, Claudia
AU  - Miele C
AD  - Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, 
      Institute of Experimental Endocrinology and Oncology, National Council of 
      Research (CNR), University of Naples Federico II, Naples, Italy.
FAU - Beguinot, Francesco
AU  - Beguinot F
AD  - Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, 
      Institute of Experimental Endocrinology and Oncology, National Council of 
      Research (CNR), University of Naples Federico II, Naples, Italy.
FAU - Formisano, Pietro
AU  - Formisano P
AD  - Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, 
      Institute of Experimental Endocrinology and Oncology, National Council of 
      Research (CNR), University of Naples Federico II, Naples, Italy.
FAU - Oriente, Francesco
AU  - Oriente F
AD  - Department of Translational Medicine, Research Unit (URT) Genomic of Diabetes, 
      Institute of Experimental Endocrinology and Oncology, National Council of 
      Research (CNR), University of Naples Federico II, Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191015
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Pknox1 protein, mouse)
RN  - 0 (Ppargc1a protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Movement/physiology
MH  - Cell Proliferation/physiology
MH  - Cells, Cultured
MH  - Endothelial Cells/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Homeodomain Proteins/*metabolism
MH  - Mice
MH  - Neovascularization, Pathologic/*metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*metabolism
OTO - NOTNLM
OT  - PGC-1alpha inhibition
OT  - TALE homeodomain proteins
OT  - p160
EDAT- 2019/10/17 06:00
MHDA- 2020/06/09 06:00
CRDT- 2019/10/17 06:00
PHST- 2019/10/17 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/10/17 06:00 [entrez]
AID - 10.1096/fj.201901230RR [doi]
PST - ppublish
SO  - FASEB J. 2019 Dec;33(12):13893-13904. doi: 10.1096/fj.201901230RR. Epub 2019 Oct 
      15.