Evidence map›Paper›PMID 25131752›Full record

ArticleThe American journal of pathology2014

Myeloid-derived tissue-type plasminogen activator promotes macrophage motility through FAK, Rac1, and NF-κB pathways.

Ling Lin, Yang Jin, Wendy M Mars, W Brian Reeves, Kebin Hu

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 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
2.1field-weighted citation impact, top 13% 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, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Activation of the NLRP3 inflammasome by RAC1 mediates a new mechanism in diabetic nephropathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. LRP-1: functions, signaling and implications in kidney and other diseases.International journal of molecular sciences · 2014
    Review
  12. Article
  13. Tissue Plasminogen Activator: Side Effects and Signaling.Journal of drug design and research · 2014
    Article
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

5 authors at 3 institutions in 1 country.

Ling LinDivision of Nephrology, Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania.
Yang JinDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Wendy M MarsDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
W Brian ReevesDivision of Nephrology, Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania.
Kebin HuDivision of Nephrology, Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania. Electronic address: kebinhu@hmc.psu.edu.
Penn State Milton S. Hershey Medical Center · USHarvard University · USUniversity of Pittsburgh · US

Funding

Epithelial/Dendritic Cell Cross-Talk in Acute Kidney InjuryR01DK081876 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI REEVES, WILLIAM BRIAN · 2009 to 2015
$2.4M
Cross talk between cav-1 and flot1 in lung injuryR01HL102076 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI JIN, YANG · 2011 to 2015
$2.1M
p90 Ribosomal S6 Kinase and Chronic Kidney DiseaseR01DK102624 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI HU, KEBIN · 2014 to 2018
$1.5M
Mechanistic insights into the systemic inflammation and organ failure in sepsisR01GM111313 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI JIN, YANG · 2014 to 2017
$1.3M
NHLBI NIH HHS R01 HL102076NIDDK NIH HHS DK081876NIDDK NIH HHS DK102624NIDDK NIH HHS R01 DK081876NIDDK NIH HHS R01 DK102624NIGMS NIH HHS R01 GM111313
6 · The paper itself

Abstract

Macrophage accumulation is one of the hallmarks of progressive kidney disease. Tissue-type plasminogen activator (tPA) is known to promote macrophage infiltration and renal inflammation during chronic kidney injury. However, the underlying mechanism remains largely unknown. We examined the role of tPA in macrophage motility in vivo by tracking fluorescence-labeled bone marrow-derived macrophages, and found that tPA-deficient mice had markedly fewer infiltrating fluorescence-labeled macrophages than the wild-type (WT) mice. Experiments in bone marrow chimeric mice further demonstrated that myeloid cells are the main source of endogenous tPA that promotes macrophage migration. In vitro studies showed that tPA promoted macrophage motility through its CD11b-mediated protease-independent function; and focal adhesion kinase (FAK), Rac-1, and NF-κB were indispensable to tPA-induced macrophage migration as either infection of FAK dominant-negative adenovirus or treatment with a Rac-1-specific inhibitor or NF-κB inhibitor abolished the effect of tPA. Moreover, ectopic FAK mimicked tPA and induced macrophage motility. tPA also activated migratory signaling in vivo. The accumulation of phospho-FAK-positive CD11b macrophages in the obstructed kidneys from WT mice was clearly attenuated in tPA knockout mice, which also displayed lower Rac-1 activity than their WT counterparts. Therefore, our results indicate that myeloid-derived tPA promotes macrophage migration through a novel signaling cascade involving FAK, Rac-1, and NF-κB.

Indexed as

Signal TransductionAnimalsCell MovementChimeraFocal Adhesion Kinase 1MacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMyeloid CellsNeuropeptidesNF-kappa Brac1 GTP-Binding ProteinTissue Plasminogen ActivatorFocal Adhesion Kinase 1NeuropeptidesNF-kappa BPtk2 protein, mouserac1 GTP-Binding ProteinRac1 protein, mouseTissue Plasminogen Activator

Identifiers

PMID25131752
PMCPMC4715214
OpenAlexW2098069966

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.