Evidence map›Paper›PMID 36672250›Full record

ArticleCells2023

PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension.

Md Khadem Ali, Xuefei Tian, Lan Zhao, Katharina Schimmel, Christopher J Rhodes, Martin R Wilkins, Mark R Nicolls, Edda F Spiekerkoetter

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

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. 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

8 authors at 3 institutions in 2 countries.

Md Khadem AliDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-1305-0413
Xuefei TianDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.
Lan ZhaoDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-2681-7695
Katharina SchimmelDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0001-7002-5113
Christopher J RhodesNational Heart and Lung Institute, Hammersmith Campus, Imperial College London, London W12 0NN, UK.ORCID 0000-0002-4962-3204
Martin R WilkinsNational Heart and Lung Institute, Hammersmith Campus, Imperial College London, London W12 0NN, UK.ORCID 0000-0003-3926-1171
Mark R NicollsDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0001-9473-7422
Edda F SpiekerkoetterDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.
Stanford University · USHammersmith Hospital · GBCardiovascular Institute of the South · US

Funding

T32 Training Program in Mechanisms and Innovation in Vascular DiseaseT32HL098049 · NHLBI · STANFORD UNIVERSITY · PI Nicholas James Leeper, Philip S Tsao · 2010 to 2026
$6.3M
Endothelial Injury, BMPR2 Dysfunction and Macrophage Activation Cause EndMT and PAHR01HL138473 · NHLBI · STANFORD UNIVERSITY · PI Mark Robert Nicolls, Marlene Rabinovitch · 2017 to 2026
$4.9M
Regulatory T Cells and Pulmonary HypertensionR01HL158714 · NHLBI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI NICOLLS, MARK ROBERT · 2021 to 2024
$2.5M
Targeting Novel BMPR2 modifiers in Pulmonary Hypertension with Repurposed DrugsR01HL128734 · NHLBI · STANFORD UNIVERSITY · PI SPIEKERKOETTER, EDDA FRAUKE · 2016 to 2020
$2.1M
BMPR2 mutations, Neointimal Transformation and Pulmonary Arterial HypertensionI01BX005628 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI Mark Robert Nicolls · 2021 to 2026
–
BLRD VA I01 BX005628British Heart Foundation FS/SBSRF/22/31025NHLBI NIH HHS R01 HL128734NHLBI NIH HHS R01 HL158714NHLBI NIH HHS T32 HL098049NIH HHS R01 HL128734
6 · The paper itself

Abstract

Bone morphogenic protein receptor 2 (BMPR2) expression and signaling are impaired in pulmonary arterial hypertension (PAH). How BMPR2 signaling is decreased in PAH is poorly understood. Protein tyrosine phosphatases (PTPs) play important roles in vascular remodeling in PAH. To identify whether PTPs modify BMPR2 signaling, we used a siRNA-mediated high-throughput screening of 22,124 murine genes in mouse myoblastoma reporter cells using ID1 expression as readout for BMPR2 signaling. We further experimentally validated the top hit, PTPN1 (PTP1B), in healthy human pulmonary arterial endothelial cells (PAECs) either silenced by siRNA or exposed to hypoxia and confirmed its relevance to PAH by measuring PTPN1 levels in blood and PAECs collected from PAH patients. We identified PTPN1 as a novel regulator of BMPR2 signaling in PAECs, which is downregulated in the blood of PAH patients, and documented that downregulation of PTPN1 is linked to endothelial dysfunction in PAECs. These findings point to a potential involvement for PTPN1 in PAH and will aid in our understanding of the molecular mechanisms involved in the disease.

Indexed as

Hypertension, PulmonaryPulmonary Arterial HypertensionVascular DiseasesAnimalsBone Morphogenetic Protein Receptors, Type IIEndothelial CellsHumansMiceProtein Tyrosine Phosphatase, Non-Receptor Type 1Pulmonary ArteryRNA, Small InterferingBMPR2 protein, humanBmpr2 protein, mouseBone Morphogenetic Protein Receptors, Type IIProtein Tyrosine Phosphatase, Non-Receptor Type 1PTPN1 protein, humanPtpn1 protein, mouseRNA, Small InterferingBMPR2 signalingendothelial dysfunctionhypoxiaPTPN1pulmonary hypertension

Identifiers

PMID36672250
PMCPMC9857213
OpenAlexW4316466040

What Socratic 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 Socratic graph.