Evidence map›Paper›PMID 26311719›Full record

ArticleCirculation research2015

MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension.

Lin Deng, Francisco J Blanco, Hannah Stevens, Ruifang Lu, Axelle Caudrillier, Martin McBride, John D McClure, Jenny Grant, Matthew Thomas, Maria Frid and 7 more

Erratum issuedAbstract read
In one paragraph

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 175 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 1 pooled it
18.2field-weighted citation impact, top 1% 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

175 citing papers in PubMed, 1 synthesis or guideline pooled it, 284 citations in OpenAlex.

  1. Pooled it
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  13. Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025
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  18. Article
  19. Harmonising cellular conversations: decoding the vital roles of extracellular vesicles in respiratory system intercellular communications.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  20. Article

115 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 2 countries.

Lin Deng *Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Francisco J Blanco *Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Hannah StevensInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Ruifang LuInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Axelle CaudrillierInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Martin McBrideInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
John D McClureInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Jenny GrantInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Matthew ThomasNovartis Institutes for BioMedical Research, Horsham UK.
Maria FridDivision of Critical Care Medicine/Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Kurt StenmarkDivision of Critical Care Medicine/Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Kevin WhiteInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Anita G SetoMiRagen Therapeutics, Inc, Boulder, CO.
Nicholas W MorrellDivision of Respiratory Medicine, Department of Medicine, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.
Angela C BradshawInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Margaret R MacLeanInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Andrew H BakerInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Novartis (United Kingdom) · GBAddenbrooke's Hospital · GBKing's College London · GBBritish Heart Foundation · GBMiragen Therapeutics (United States) · USUniversity of Cambridge · GB

Funding

VRAC and Rho in pulmonary EC proliferationP01HL014985 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI STENMARK, KURT R. · 1985 to 2019
$35.1M
Fibroblasts and Mononuclear Fibrogenic Cells Drive Right Ventricular Pulmonary ArR01HL114887 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BULL, TODD M, BUTTRICK, PETER N. · 2012 to 2016
$3.4M
British Heart Foundation CH/11/2/28733British Heart Foundation RG/13/4/30107British Heart Foundation SP/12/9/29593European Research Council 338991Medical Research Council G0800784Medical Research Council G1000847NHLBI NIH HHS P01 HL014985NHLBI NIH HHS R01 HL114887
6 · The paper itself

Abstract

rationaleThe pathogenesis of pulmonary arterial hypertension (PAH) remains unclear. The 4 microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered.

objectiveTo elucidate the transcriptional regulation of the miR-143/145 cluster and the role of miR-143 in PAH. METHODS AND

resultsWe identified the promoter region that regulates miR-143/145 microRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signaling pathways, including estrogen receptor, liver X factor/retinoic X receptor, transforming growth factor-β (Smads), and hypoxia (hypoxia response element), that regulated levels of all pri-miR stem loop transcription and resulting microRNA expression. We observed that miR-143-3p is selectively upregulated compared with miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMC-derived exosomes. Using assays with pulmonary arterial endothelial cells, we demonstrated a paracrine promigratory and proangiogenic effect of miR-143-3p-enriched exosomes from PASMC. Quantitative polymerase chain reaction and in situ hybridization showed elevated expression of miR-143 in calf models of PAH and in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role of miR-143 in experimental pulmonary hypertension in vivo in miR-143-/- and anti-miR-143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings.

conclusionsMiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, whereas inhibition of miR-143-3p blocked experimental pulmonary hypertension. Taken together, these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology.

Indexed as

Cell CommunicationAnimalsArterial PressureBinding SitesCase-Control StudiesCattleCell MovementEndothelial CellsExosomesFemaleGene Expression RegulationHeLa CellsHumansHypertension, PulmonaryMaleMice, Inbred C57BLMicroRNAsMIRN143 microRNA, humanMIRN143 microRNA, mouseMIRN145a microRNA, mouseMIRN145 microRNA, humanTranscription Factorscell movementendotheliumexosomeshypertension, pulmonarymicroRNAsmyocytes, smooth muscle

Identifiers

PMID26311719
PMCPMC4620852
OpenAlexW1954145299

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.