Evidence map›Paper›PMID 34551592›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2021

Receptor and Molecular Mechanism of AGGF1 Signaling in Endothelial Cell Functions and Angiogenesis.

Jingjing Wang, Huixin Peng, Ayse Anil Timur, Vinay Pasupuleti, Yufeng Yao, Teng Zhang, Sun-Ah You, Chun Fan, Yubing Yu, Xinzhen Jia and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
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  12. AGGF1 Shows the α5β1 Integrin to Be AnotherArteriosclerosis, thrombosis, and vascular biology · 2021
    Article
  13. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 3 countries.

Jingjing Wang *Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).
Huixin Peng *Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).
Ayse Anil Timur *Robert J. Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic, OH (A.A.T.).
Vinay Pasupuleti *Departments of Molecular Cardiology and Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (A.A.T., V.P., S.-A.Y., C.F., Q.C., Q.W.).
Yufeng Yao *Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).
Teng Zhang *Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, China (T.Z.).
Sun-Ah You *Departments of Molecular Cardiology and Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (A.A.T., V.P., S.-A.Y., C.F., Q.C., Q.W.).
Chun Fan *Departments of Molecular Cardiology and Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (A.A.T., V.P., S.-A.Y., C.F., Q.C., Q.W.).
Yubing Yu *Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).
Xinzhen JiaKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).
Jing ChenKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).
Chengqi XuKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).ORCID 0000-0002-4269-6830
Qiuyun ChenDepartments of Molecular Cardiology and Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (A.A.T., V.P., S.-A.Y., C.F., Q.C., Q.W.).ORCID 0000-0002-3645-400X
Qing WangKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China (J.W., H.P., Y. Yao, Y. Yu, X.J., J.C., C.X., Q.W.).ORCID 0000-0002-2235-6572
Ministry of Education · KRCleveland Clinic Lerner College of Medicine · USYonsei University · KRKent State University · USCleveland Clinic · USShanghai University of Traditional Chinese Medicine · CN

Funding

The Role of Thrombospondins in AtherothrombosisP50HL077107 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI LAUER, MICHAEL S · 2005 to 2009
$16.5M
Molecular Mechanisms of Cardiac ArrhythmiasR01HL066251 · NHLBI · CLEVELAND CLINIC LERNER COL/MED-CWRU · PI WANG, QING KENNETH · 2002 to 2005
$1.7M
NHLBI NIH HHS P50 HL077107NHLBI NIH HHS R01 HL066251
6 · The paper itself

Abstract

Objective: Angiogenic factor AGGF1 (angiogenic factor with G-patch and FHA [Forkhead-associated] domain 1) promotes angiogenesis as potently as VEGFA (vascular endothelial growth factor A) and regulates endothelial cell (EC) proliferation, migration, specification of multipotent hemangioblasts and venous ECs, hematopoiesis, and vascular development and causes vascular disease Klippel-Trenaunay syndrome when mutated. However, the receptor for AGGF1 and the underlying molecular mechanisms remain to be defined. Approach and Results: Using functional blocking studies with neutralizing antibodies, we identified [alpha]5[beta]1 as the receptor for AGGF1 on ECs. AGGF1 interacts with [alpha]5[beta]1 and activates FAK (focal adhesion kinase), Src (proto-oncogene tyrosine-protein kinase), and AKT (protein kinase B). Functional analysis of 12 serial N-terminal deletions and 13 C-terminal deletions by every 50 amino acids mapped the angiogenic domain of AGGF1 to a domain between amino acids 604-613 (FQRDDAPAS). The angiogenic domain is required for EC adhesion and migration, capillary tube formation, and AKT activation. The deletion of the angiogenic domain eliminated the effects of AGGF1 on therapeutic angiogenesis and increased blood flow in a mouse model for peripheral artery disease. A 40-mer or 15-mer peptide containing the angiogenic domain blocks AGGF1 function, however, a 15-mer peptide containing a single amino acid mutation from -RDD- to -RGD- (a classical RGD integrin-binding motif) failed to block AGGF1 function. Conclusions: We have identified integrin [alpha]5[beta]1 as an EC receptor for AGGF1 and a novel AGGF1-mediated signaling pathway of [alpha]5[beta]1-FAK-Src-AKT for angiogenesis. Our results identify an FQRDDAPAS angiogenic domain of AGGF1 crucial for its interaction with [alpha]5[beta]1 and signaling.

Indexed as

Neovascularization, Physiologic3T3-L1 CellsAngiogenesis Inducing AgentsAngiogenic ProteinsAnimalsDisease Models, AnimalEndothelial CellsFemaleFocal Adhesion Kinase 1HEK293 CellsHeLa CellsHep G2 CellsHindlimbHumansIntegrin alpha5beta1IschemiaAGGF1 protein, humanAggf1 protein, mouseAngiogenesis Inducing AgentsAngiogenic ProteinsFocal Adhesion Kinase 1Integrin alpha5beta1LigandsMAS1 protein, humanPeptide FragmentsProto-Oncogene MasProto-Oncogene Proteins c-aktPTK2 protein, humanPtk2 protein, mousesrc-Family Kinasesamino acidsendothelial cellshemangioblastsintegrinsperipheral artery disease

Identifiers

PMID34551592
PMCPMC8580577
OpenAlexW3200587852

What Socratic holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.