Evidence map›Paper›PMID 32061928›Full record

ArticleJournal of molecular biology2020

Homeobox D3, A Novel Link Between Bone Morphogenetic Protein 9 and Transforming Growth Factor Beta 1 Signaling.

Lumin Wang, Jiayi Yao, Tongtong Yu, Daoqin Zhang, Xiaojing Qiao, Zehao Yao, Xiuju Wu, Li Zhang, Kristina I Boström, Yucheng Yao

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

Article in Journal of molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Lumin WangDepartment of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China; Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA.
Jiayi YaoDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA.
Tongtong YuDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA; Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
Daoqin ZhangDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA.
Xiaojing QiaoDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA.
Zehao YaoDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA; College of Life Science, Nankai University, Tianjin, China.
Xiuju WuDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA.
Li ZhangDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA.
Kristina I BoströmDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA; The Molecular Biology Institute at UCLA, Los Angeles, CA, 90095-1570, USA. Electronic address: kbostrom@mednet.ucla.edu.
Yucheng YaoDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA. Electronic address: yyao@mednet.ucla.edu.
University of California, Los Angeles · USChina Medical University · CNXi'an Jiaotong University · CN

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Molecular Mechanisms of MGP; Role in AVMsR01HL081397 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOSTROM, KRISTINA I · 2006 to 2025
$7.7M
BMP and Notch Crosstalk in Cerebral Arteriovenous MalformationsR01NS079353 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yucheng Yao · 2012 to 2026
$5.3M
Switch of Osteogenesis in Vascular CalcificationR01HL139675 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yucheng Yao · 2018 to 2026
$3.6M
NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL081397NHLBI NIH HHS R01 HL139675NINDS NIH HHS R01 NS079353
6 · The paper itself

Abstract

aimsSeveral signaling pathways contribute to endothelial-mesenchymal transitions and vascular calcification, including bone morphogenetic protein (BMP) and transforming growth factor (TGF) β signaling. The transcription factor homeobox D3 (Hoxd3) is known to regulate an invasive endothelial phenotype, and the aim of the study is to determine if HOXD3 modulates BMP and TGFβ signaling in the endothelium. METHODS AND RESEARCH: We report that the endothelium with high BMP activity due to the loss of BMP inhibitor matrix Gla protein (MGP) shows induction of Hoxd3. HOXD3 is part of a BMP-triggered cascade. When activated by BMP9, activin receptor-like kinase (ALK) 1 induces HOXD3 expression. Hoxd3 promoter is a direct target of phosphorylated (p) SMAD1, a mediator of BMP signaling. High BMP activity further results in enhanced TGFβ signaling due to induction of TGFβ1 and its receptor, ALK5. This is mediated by HOXD3, which directly targets the Tgfb1 promoter. Finally, TGFβ1 and BMP9 stimulate the expression of MGP, which limits the enhanced ALK1 induction by counteracting BMP4. The cascade of BMP9-HOXD3-TGFβ also affects Notch signaling and angiogenesis through induction of Notch ligand Jagged 2 and suppression of Notch ligand delta-like 4 (Dll4).

conclusionThe results suggest that HOXD3 is a novel link between BMP9/ALK1 and TGFβ1/ALK5 signaling. TRANSLATIONAL PERSPECTIVE: BMP and TGFβ signaling are instrumental in vascular disease such as vascular calcification and atherosclerosis. This study demonstrated a novel type of cross talk between endothelial BMP and TGFβ signaling as mediated by HOXD3. The results provide a possible therapeutic approach to control dysfunctional BMP and TGFβ signaling by regulating HOXD3.

Indexed as

Neovascularization, PhysiologicActivin Receptors, Type IIAnimalsDNA-Binding ProteinsEndothelium, VascularGene Expression RegulationGrowth Differentiation Factor 2HumansHuman Umbilical Vein Endothelial CellsMiceMice, Inbred C57BLMice, KnockoutPhosphorylationProteinsReceptors, NotchSignal TransductionActivin Receptors, Type IIAcvrl1 protein, mouseDNA-Binding ProteinsGdf2 protein, mousegranuloma protein, mouseGrowth Differentiation Factor 2Hoxd3 protein, mouseProteinsReceptors, NotchTgfb1 protein, mouseTransforming Growth Factor beta1activin receptor-like kinase 1bone morphogenetic proteinendotheliumNotchvascular development

Identifiers

PMID32061928
PMCPMC7225048
OpenAlexW3006342274

What OpenQuestion holds

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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 OpenQuestion graph.