Evidence map›Paper›PMID 34921404›Full record

ArticleThe Journal of physiology2022

Notch1 promotes ordered revascularization through Semaphorin 3g modulation of downstream vascular patterning signalling factors.

James Hyun, Monica Lee, Jalees Rehman, Kostandin V Pajcini, Asrar B Malik

Open access · hybridAbstract read
In one paragraph

Article in The Journal of physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 45% 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

4 citing papers in PubMed, 6 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

5 authors at 1 institution in 1 country.

James HyunDepartment of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, USA.
Monica LeeDepartment of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, IL, USA.
Jalees RehmanDepartment of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, USA.
Kostandin V PajciniDepartment of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, USA.
Asrar B MalikDepartment of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, USA.ORCID 0000-0002-8205-7128
Illinois College · US

Funding

Strengthening Stakeholder Engagement in Human Research Protections.UL1TR002003 · NCATS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARNIK, NIRANJAN SUBHASH, MERMELSTEIN, ROBIN J. · 2016 to 2024
$33.7M
Trpm2 Regulation of Phagocyte Bactericidal Activity and Resolution of Lung InjuryP01HL077806 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2005 to 2019
$27.0M
TRAINING PROGRAM IN LUNG BIOLOGY AND PATHOBIOLOGYT32HL007829 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DOLLY MEHTA · 1995 to 2026
$15.6M
The role of Notch signaling in fetal hematopoietic stem cellsR01HL134971 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PAJCINI, KOSTANDIN · 2017 to 2021
$2.2M
National Centre for Advancing Translational Sciences, National Institutes of Health UL1TR002003NCATS NIH HHS UL1 TR002003NHLBI NIH HHS P01 HL077806NHLBI NIH HHS R01 HL134971NHLBI NIH HHS T32 HL007829NIH HHS P01HL077806NIH HHS R01HL134971NIH HHS T32HL007829
6 · The paper itself

Abstract

Here we genetically and functionally addressed potential pathways of Notch signalling in mediating vascular regeneration in mouse models. We first used transgenic adult mice with either gain- or loss-of-function Notch signalling in vascular endothelial cells and monitored perfusion in the hindlimb following ischaemia induced by femoral artery ligation. Mice deficient in Notch signalling showed defective perfusion recovery and expansion of collateral arteries. Transcriptomics analysis of arterial endothelial cells in the Notch mutants identified the guidance factor Sema3g as a candidate gene mediating reperfusion downstream of Notch. Studies in the retinal circulation showed the central role of SEMA3G downstream of Notch signalling in the orderly regulation of vascular patterning. These studies in multiple vascular beds show the primacy of Notch signalling and downstream generation of guidance peptides such as SEMA3G in promoting well-ordered vascular regeneration. KEY POINTS: Notch signalling is a critical mediator of revascularization. Yet the cellular processes activated during recovery following vascular injury are incompletely understood. Here we used genetic and cellular approaches in two different vascular beds and cultured endothelial cells to address the generalizability of mechanisms. By utilizing a highly reproducible murine model of hindlimb ischaemia in transgenic mice in which Notch signalling was inhibited at the transcriptional level, we demonstrated the centrality of Notch signalling in perfusion recovery and revascularization. RNA-sequencing of Notch mutants identified class 3 Semaphorins regulated by Notch signalling as downstream targets. Studies in retinal vessels and endothelial cells showed an essential role of guidance peptide Sema3g as a modulator of angiogenesis and orderly vascular patterning. The Notch to Sema3g signalling axis functions as a feedback mechanism to sculpt the growing vasculature in multiple beds.

Indexed as

SemaphorinsAnimalsEndothelial CellsHindlimbMiceNeovascularization, PhysiologicReceptor, Notch1Receptors, NotchSignal TransductionNotch1 protein, mouseReceptor, Notch1Receptors, Notchsemaphorin 3G, mouseSemaphorinsangiogenesisarteriogenesisischaemic injurynotch signalingvascular biology

Identifiers

PMID34921404
PMCPMC9305962
OpenAlexW4200136676

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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.