Evidence map›Paper›PMID 32502201›Full record

ArticlePLoS biology2020

Targeting miR-27a/VE-cadherin interactions rescues cerebral cavernous malformations in mice.

Jia Li, Yang Zhao, Jaesung Choi, Ka Ka Ting, Paul Coleman, Jinbiao Chen, Victoria C Cogger, Li Wan, Zhongsong Shi, Thorleif Moller and 3 more

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

Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Modulation of miR-23b Wnt/β-catenin Axis Strengthens Endothelial Barrier Properties.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Endothelial estrogen receptor alpha (ESR1) regulates cerebral cavernous malformation pathogenesis via MEKK3-KLF signaling pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Article
  6. Endothelial lincRNA-p21 alleviates cerebral ischemia/reperfusion injury by maintaining blood-brain barrier integrity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  7. Review
  8. Article
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  11. Article
  12. Review
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  17. Development of Novel Therapeutics Targeting the Blood-Brain Barrier: From Barrier to Carrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
  18. Review
  19. Review
  20. Review
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 2 institutions in 2 countries.

Jia LiCentre for the Endothelium, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.ORCID 0000-0003-1166-1288
Yang ZhaoCentre for the Endothelium, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.
Jaesung ChoiLaboratory of Cardiovascular Signaling, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.ORCID 0000-0002-0135-8632
Ka Ka TingCentre for the Endothelium, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.
Paul ColemanCentre for the Endothelium, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.
Jinbiao ChenLiver Injury and Cancer Program, Centenary Institute, The University of Sydney, Sydney, Australia.
Victoria C CoggerAging and Alzheimers Institute and ANZAC Research Institute and Concord Hospital, Charles Perkins Centre, The University of Sydney, Sydney, Australia.
Li WanCentre for the Endothelium, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.
Zhongsong ShiDepartment of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Thorleif MollerRanger Biotechnologies A/S, Arslev, Denmark.ORCID 0000-0002-5006-4673
Xiangjian ZhengLaboratory of Cardiovascular Signaling, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.ORCID 0000-0001-6277-5168
Mathew A VadasCentre for the Endothelium, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.
Jennifer R GambleCentre for the Endothelium, Vascular Biology Program, Centenary Institute, The University of Sydney, Sydney, Australia.ORCID 0000-0002-0179-9964
The University of Sydney · AUSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cerebral cavernous malformations (CCMs) are vascular lesions predominantly developing in the central nervous system (CNS), with no effective treatments other than surgery. Loss-of-function mutation in CCM1/krev interaction trapped 1 (KRIT1), CCM2, or CCM3/programmed cell death 10 (PDCD10) causes lesions that are characterized by abnormal vascular integrity. Vascular endothelial cadherin (VE-cadherin), a major regulator of endothelial cell (EC) junctional integrity is strongly disorganized in ECs lining the CCM lesions. We report here that microRNA-27a (miR-27a), a negative regulator of VE-cadherin, is elevated in ECs isolated from mouse brains developing early CCM lesions and in cultured ECs with CCM1 or CCM2 depletion. Furthermore, we show miR-27a acts downstream of kruppel-like factor (KLF)2 and KLF4, two known key transcription factors involved in CCM lesion development. Using CD5-2 (a target site blocker [TSB]) to prevent the miR-27a/VE-cadherin mRNA interaction, we present a potential therapy to increase VE-cadherin expression and thus rescue the abnormal vascular integrity. In CCM1- or CCM2-depleted ECs, CD5-2 reduces monolayer permeability, and in Ccm1 heterozygous mice, it restores dermal vessel barrier function. In a neonatal mouse model of CCM disease, CD5-2 normalizes vasculature and reduces vascular leakage in the lesions, inhibits the development of large lesions, and significantly reduces the size of established lesions in the hindbrain. Furthermore, CD5-2 limits the accumulation of inflammatory cells in the lesion area. Our work has established that VE-cadherin is a potential therapeutic target for normalization of the vasculature and highlights that targeting miR-27a/VE-cadherin interaction by CD5-2 is a potential novel therapy for the devastating disease, CCM.

Indexed as

AnimalsAntigens, CDCadherin 5CadherinsDown-RegulationHemangioma, Cavernous, Central Nervous SystemHumansHuman Umbilical Vein Endothelial CellsKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMice, Inbred C57BLMicroRNAsrhoA GTP-Binding ProteinRhombencephalonUp-RegulationAntigens, CDCadherin 5CadherinsKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsMicroRNAsMirn27 microRNA, mouserhoA GTP-Binding Protein

Identifiers

PMID32502201
PMCPMC7299406
OpenAlexW3034055926

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.