Evidence map›Paper›PMID 33765345›Full record

ArticleHepatology (Baltimore, Md.)2021

CD47-Mediated Hedgehog/SMO/GLI1 Signaling Promotes Mesenchymal Stem Cell Immunomodulation in Mouse Liver Inflammation.

Mingwei Sheng, Yuanbang Lin, Dongwei Xu, Yizhu Tian, Yongqiang Zhan, Changyong Li, Douglas G Farmer, Jerzy W Kupiec-Weglinski, Bibo Ke

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

Article in Hepatology (Baltimore, Md.), 2021. 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
3.8field-weighted citation impact, top 5% 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, 61 citations in OpenAlex.

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  13. Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024
    Review
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  15. Article
  16. Endoplasmic reticulum aminopeptidase 2 regulates CD4Arthritis research & therapy · 2024
    Article
  17. Article
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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 at 1 institution in 2 countries.

Mingwei Sheng *Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.
Yuanbang Lin *Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.
Dongwei Xu *Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.ORCID 0000-0001-9802-0664
Yizhu TianDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.
Yongqiang ZhanDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.
Changyong LiDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.
Douglas G FarmerDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.
Jerzy W Kupiec-WeglinskiDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.
Bibo KeDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, the Dumont-UCLA Transplant Center, Los Angeles, CA.ORCID 0000-0002-1885-1538
University of California, Los Angeles · US

Funding

Regulation of Innate Immune Responses by Alloimmunity in Liver Ischemia-Reperfusion InjuryP01AI120944 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jerzy W Kupiec-Weglinski · 2017 to 2026
$20.0M
NRF2 - SIRT1 SIGNALING AXIS IN LIVER TRANSPLANT REJUVENATIONR01DK062357 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2003 to 2025
$8.4M
Innate Immune Regulation by HSF1 in Liver Inflammatory InjuryR01AI139552 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO · 2019 to 2023
$1.9M
CD47-SIRPalpha Signaling in Mesenchymal Stem Cell-Mediated Immune Regulation in Liver Transplant Inflammatory InjuryR21AI146742 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO · 2019 to 2020
$429k
Immune Regulation by Stem Cells: Role of Beta-Catenin in Liver Inflammatory InjuryR21AI115133 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO, KUPIEC-WEGLINSKI, JERZY W · 2017 to 2018
$428k
Beta-Catenin Signaling in Liver Ischemia and Reperfusion InjuryR21AI112722 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO, KUPIEC-WEGLINSKI, JERZY W · 2014 to 2015
$385k
NIAID NIH HHS P01 AI120944NIAID NIH HHS R01 AI139552NIAID NIH HHS R21 AI112722NIAID NIH HHS R21 AI115133NIAID NIH HHS R21 AI146742NIDDK NIH HHS R01 DK062357
6 · The paper itself

Abstract

BACKGROUND AND

aimsThe cluster of differentiation 47 (CD47)-signal regulatory protein alpha (SIRPα) signaling pathway plays important roles in immune homeostasis and tissue inflammatory response. Activation of the Hedgehog/smoothened (SMO)/GLI family zinc finger 1 (Gli1) pathway regulates cell growth, differentiation, and immune function. However, it remains unknown whether and how the CD47-SIRPα interaction may regulate Hedgehog/SMO/Gli1 signaling in mesenchymal stem cell (MSC)-mediated immune regulation during sterile inflammatory liver injury. APPROACH AND

resultsIn a mouse model of ischemia/reperfusion (IR)-induced sterile inflammatory liver injury, we found that adoptive transfer of MSCs increased CD47 expression and ameliorated liver IR injury. However, deletion of CD47 in MSCs exacerbated IR-induced liver damage, with increased serum ALT levels, macrophage/neutrophil infiltration, and pro-inflammatory mediators. MSC treatment augmented SIRPα, Hedgehog/SMO/Gli1, and Notch1 intracellular domain (NICD), whereas CD47-deficient MSC treatment reduced these gene expressions in IR-stressed livers. Moreover, disruption of myeloid SMO or Notch1 increased IR-triggered liver inflammation with diminished Gli1 and NICD, but enhanced NIMA related kinase 7 (NEK7) and NLR family pyrin domain containing 3 (NLRP3) activation in MSC-transferred mice. Using a MSC/macrophage co-culture system, we found that MSC CD47 and macrophage SIRPα expression were increased after LPS stimulation. The CD47-SIRPα interaction increased macrophage Gli1 and NICD nuclear translocation, whereby NICD interacted with Gli1 and regulated its target gene Dvl2 (dishevelled segment polarity protein 2), which in turn inhibited NEK7/NLRP3 activity.

conclusionsThe CD47-SIRPα signaling activates the Hedgehog/SMO/Gli1 pathway, which controls NEK7/NLRP3 activity through a direct interaction between Gli1 and NICD. NICD is a coactivator of Gli1, and the target gene Dvl2 regulated by the NICD-Gli1 complex is crucial for the modulation of NLRP3-driven inflammatory response in MSC-mediated immune regulation. Our findings provide potential therapeutic targets in MSC-mediated immunotherapy of sterile inflammatory liver injury.

Indexed as

Alanine TransaminaseAnimalsCD47 AntigenDishevelled ProteinsHedgehog ProteinsInflammationLiverMacrophagesMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMiceNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Notch1Receptors, ImmunologicReperfusion InjuryAlanine TransaminaseCD47 AntigenCd47 protein, mouseDishevelled ProteinsDvl2 protein, mouseGli1 protein, mouseHedgehog ProteinsNek7 protein, mouseNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseNotch1 protein, mouseReceptor, Notch1Receptors, ImmunologicSirpa protein, mouseSmoothened ReceptorSmo protein, mouseZinc Finger Protein GLI1

Identifiers

PMID33765345
PMCPMC9436023
OpenAlexW3136671672

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.