Evidence map›Paper›PMID 24220290›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2014

TGFβ-Mediated Downregulation of Thrombopoietin Is Associated With Platelet Decline in Asymptomatic SIV Infection.

Kelly A Metcalf Pate, Claire E Lyons, Jamie L Dorsey, Suzanne E Queen, Robert J Adams, Craig N Morrell, Joseph L Mankowski

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

13 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Thrombocytopenia in Virus Infections.Journal of clinical medicine · 2021
    Review
  10. Article
  11. Article
  12. Review
  13. 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

7 authors at 3 institutions in 1 country.

Kelly A Metcalf Pate*Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD; †Aab Cardiovascular Research Institute, School of Medicine and Dentistry, University of Rochester, Rochester, NY; ‡Department of Pathology; and §Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
Claire E Lyons
Jamie L Dorsey
Suzanne E Queen
Robert J Adams
Craig N Morrell
Joseph L Mankowski
Johns Hopkins University · USJohns Hopkins Medicine · USUniversity of Rochester · US

Funding

Training Veterinarians for Careers in Biomedical ResearchT32OD011089 · OD · JOHNS HOPKINS UNIVERSITY · PI JOSEPH L MANKOWSKI · 2012 to 2026
$6.7M
Development of an SPF Macaca nemestrina Breeding ColonyP40OD013117 · OD · JOHNS HOPKINS UNIVERSITY · PI ADAMS, ROBERT J. · 2012 to 2016
$4.9M
Translational Research in Neuro-AIDS and Mental HealthR25MH080661 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MCARTHUR, JUSTIN CHARLES. · 2007 to 2019
$2.9M
Viral Host Interactions in SIV Cardiac DysfunctionR01HL078479 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MANKOWSKI, JOSEPH L · 2004 to 2008
$2.7M
NHLBI NIH HHS R01 HL078479NIH HHS P40 OD013117NIH HHS T32 OD011089NIMH NIH HHS R25 MH080661
6 · The paper itself

Abstract

backgroundThrombocytopenia is a known consequence of HIV infection, and decreased production of platelets has been previously implicated in the pathogenesis of platelet decline during asymptomatic infection. Thrombopoietin (THPO) drives platelet production by stimulating the maturation of bone marrow megakaryocytes and can be transcriptionally downregulated by cytokines that are increased during infection such as transforming growth factor β (TGFβ) and platelet factor 4 (pf4).

designTo determine whether transcriptional downregulation of THPO contributed to decreased platelet production during asymptomatic infection in the simian immunodeficiency virus (SIV)/macaque model of HIV, we compared hepatic THPO mRNA levels to platelet number and megakaryocyte density. To identify potential inhibitory factors that decrease THPO transcription during asymptomatic infection, we measured TGFβ and pf4 plasma levels. To determine whether combined antiretroviral therapy (cART) could correct platelet decline by altering cytokine levels, we measured TGFβ and pf4 in cART-treated SIV-infected macaques and compared these values to cART-untreated SIV-infected macaques.

resultsHepatic THPO transcription was downregulated during asymptomatic SIV infection concurrent with platelet decline. Hepatic THPO mRNA levels correlated with bone marrow megakaryocyte density. In contrast, plasma TGFβ levels were inversely correlated with hepatic THPO transcription and bone marrow megakaryocyte density. With cART treatment, plasma TGFβ levels and platelet count returned to values similar to those in uninfected macaques.

conclusionsTGFβ-mediated downregulation of hepatic THPO may lead to decline in platelet number during asymptomatic SIV infection, and cART may prevent platelet decline by normalizing plasma TGFβ levels.

Indexed as

ThrombocytopeniaThrombopoiesisAnimalsAnti-Retroviral AgentsAsymptomatic DiseasesDown-RegulationGene Expression ProfilingLiverMacaca nemestrinaMaleMegakaryocytesPlatelet CountSimian Acquired Immunodeficiency SyndromeThrombopoietinTransforming Growth Factor betaTreatment OutcomeAnti-Retroviral AgentsThrombopoietinTransforming Growth Factor beta

Identifiers

PMID24220290
PMCPMC3999250
OpenAlexW2328264724

What OpenQuestion holds

Textmetadata
LicenceTDM
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.