Evidence map›Paper›PMID 37480504›Full record

ArticleCellular and molecular life sciences : CMLS2023

Kindlin-2 controls angiogenesis through modulating Notch1 signaling.

Yuechao Dong, Guixing Ma, Xiaoting Hou, Yingying Han, Zhen Ding, Wanze Tang, Litong Chen, Yangshan Chen, Bo Zhou, Feng Rao and 3 more

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

Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

8 citing papers in PubMed, 13 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

13 authors at 1 institution in 1 country.

Yuechao Dong *Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Guixing Ma *Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China. maguixing@live.com.
Xiaoting Hou *Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Yingying Han *Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Zhen DingDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Wanze TangDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Litong ChenDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Yangshan ChenDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Bo ZhouDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Feng RaoSouthern University of Science and Technology, Shenzhen, 518055, China.
Kaosheng LvDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Changzheng DuDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Huiling CaoDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China. caohl@sustech.edu.cn.ORCID http://orcid.org/0000-0002-7728-1774
Southern University of Science and Technology · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we report that sufficient KINDLIN-2 is extremely important for NOTCH-mediated physiological angiogenesis. The expression of KINDLIN-2 in HUVECs is significantly modulated by angiogenic factors such as vascular endothelial growth factor A or tumor necrosis factor α. A strong co-localization of CD31 and Kindlin-2 in tissue sections is demonstrated by immunofluorescence staining. Endothelial-cell-specific Kindlin-2 deletion embryos die on E10.5 due to hemorrhage caused by the impaired physiological angiogenesis. Experiments in vitro show that vascular endothelial growth factor A-induced multiple functions of endothelial cells, including migration, matrix proteolysis, morphogenesis and sprouting, are all strengthened by KINDLIN-2 overexpression and severely impaired in the absence of KINDLIN-2. Mechanistically, we demonstrate that KINDLIN-2 inhibits the release of Notch intracellular domain through binding to and maintaining the integrity of NOTCH1. The impaired angiogenesis and avascular retinas caused by KINDLIN-2 deficiency can be rescued by DAPT, an inhibitor of γ-secretase which releases the intracellular domain from NOTCH1. Moreover, we demonstrate that high glucose stimulated hyperactive angiogenesis by increasing KINDLIN-2 expression could be prevented by KINDLIN-2 knockdown, indicating Kindlin-2 as a potential therapeutic target in treatment of diabetic retinopathy. Our study for the first time demonstrates the significance of Kindlin-2 in determining Notch-mediated angiogenesis during development and highlights Kindlin-2 as the potential therapeutic target in angiogenic diseases, such as diabetic retinopathy.

Indexed as

Diabetic RetinopathyCardiovascular Physiological PhenomenaEndothelial CellsHumansMembrane ProteinsMorphogenesisNeoplasm ProteinsReceptor, Notch1Vascular Endothelial Growth Factor AFERMT3 protein, humanMembrane ProteinsNeoplasm ProteinsNOTCH1 protein, humanReceptor, Notch1Vascular Endothelial Growth Factor AAngiogenesisEndothelial Kindlin-2NICDNotch1

Identifiers

PMID37480504
PMCPMC11072286
OpenAlexW4385146428

What OpenQuestion holds

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Registered trials

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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.