Evidence map›Paper›PMID 25250571›Full record

ArticleThe Journal of clinical investigation2014

Pleiotrophin mediates hematopoietic regeneration via activation of RAS.

Heather A Himburg, Xiao Yan, Phuong L Doan, Mamle Quarmyne, Eva Micewicz, William McBride, Nelson J Chao, Dennis J Slamon, John P Chute

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

32 citing papers in PubMed, 58 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

9 authors.

Heather A Himburg
Xiao Yan
Phuong L Doan
Mamle Quarmyne
Eva Micewicz
William McBride
Nelson J Chao
Dennis J Slamon
John P Chute

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
Somatostatin analogues as countermeasures against intestinal radiation toxicityU19AI067798 · NIAID · DUKE UNIVERSITY · PI DOAN, PHUONG LINH · 2005 to 2024
$82.1M
ORGANIZATION AND FUNCTIONS OF CELLULAR STRUCTUREST32GM007184 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1985 to 2019
$18.2M
Semaphorin signaling regulates vascular and hematopoietic regenerationR01HL086998 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P · 2008 to 2022
$4.6M
Role of ErbB receptor signaling in regulating normal and leukemic stem cell fateK08CA184552 · NCI · DUKE UNIVERSITY · PI DOAN, PHUONG LINH · 2014 to 2018
$639k
NCI NIH HHS K08 CA184552NCI NIH HHS P30 CA014236NHLBI NIH HHS HL-086998NHLBI NIH HHS R01 HL086998NIAID NIH HHS AI-067798NIAID NIH HHS U19 AI067798NIGMS NIH HHS T32 GM007184
6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) are highly susceptible to ionizing radiation-mediated death via induction of ROS, DNA double-strand breaks, and apoptotic pathways. The development of therapeutics capable of mitigating ionizing radiation-induced hematopoietic toxicity could benefit both victims of acute radiation sickness and patients undergoing hematopoietic cell transplantation. Unfortunately, therapies capable of accelerating hematopoietic reconstitution following lethal radiation exposure have remained elusive. Here, we found that systemic administration of pleiotrophin (PTN), a protein that is secreted by BM-derived endothelial cells, substantially increased the survival of mice following radiation exposure and after myeloablative BM transplantation. In both models, PTN increased survival by accelerating the recovery of BM hematopoietic stem and progenitor cells in vivo. PTN treatment promoted HSC regeneration via activation of the RAS pathway in mice that expressed protein tyrosine phosphatase receptor-zeta (PTPRZ), whereas PTN treatment did not induce RAS signaling in PTPRZ-deficient mice, suggesting that PTN-mediated activation of RAS was dependent upon signaling through PTPRZ. PTN strongly inhibited HSC cycling following irradiation, whereas RAS inhibition abrogated PTN-mediated induction of HSC quiescence, blocked PTN-mediated recovery of hematopoietic stem and progenitor cells, and abolished PTN-mediated survival of irradiated mice. These studies demonstrate the therapeutic potential of PTN to improve survival after myeloablation and suggest that PTN-mediated hematopoietic regeneration occurs in a RAS-dependent manner.

Indexed as

HematopoiesisAnimalsBone Marrow TransplantationCarrier ProteinsCells, CulturedCytokinesMiceRadiation Injuries, Experimentalras ProteinsRegenerationSignal TransductionCarrier ProteinsCytokinespleiotrophinras Proteins

Identifiers

PMID25250571
PMCPMC4347246
OpenAlexW2093617531

What OpenQuestion holds

Textmetadata
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.