Evidence map›Paper›PMID 30194990›Full record

ArticleThe Journal of allergy and clinical immunology2019

Ras homolog family member A/Rho-associated protein kinase 1 signaling modulates lineage commitment of mesenchymal stem cells in asthmatic patients through lymphoid enhancer-binding factor 1.

Xia Ke, Danh C Do, Changjun Li, Yilin Zhao, Marian Kollarik, Qingling Fu, Mei Wan, Peisong Gao

Abstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

28 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
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  4. Distribution, contribution and regulation of nestinJournal of advanced research · 2024
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  10. Article
  11. Nestin promotes pulmonary fibrosisThe European respiratory journal · 2022
    Article
  12. Article
  13. Bioengineered · 2022
    Article
  14. Article
  15. TThe Journal of allergy and clinical immunology · 2022
    Article
  16. Rho Kinases in Embryonic Development and Stem Cell Research.Archivum immunologiae et therapiae experimentalis · 2022
    Review
  17. Article
  18. Review
  19. Review
  20. 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

8 authors at 4 institutions in 2 countries.

Xia KeDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md; Department of Otorhinolaryngology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Danh C DoDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
Changjun LiDepartment of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Md.
Yilin ZhaoDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md; Department of Respiratory Medicine, Fourth Military Medical University, Xi'an, China.
Marian KollarikDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
Qingling FuOtorhinolaryngology Hospital, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Mei WanDepartment of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Md.
Peisong GaoDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: pgao1@jhmi.edu.
Johns Hopkins University · USAir Force Medical University · CNJohns Hopkins Medicine · USSun Yat-sen University · CN

Funding

Sensitization to Cockroach Allergen: Immune Regulation and Genetic DeterminantsR01ES021739 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2013 to 2017
$1.8M
Mannose Receptor, miR-511-3p, and Macrophage Polarization in AsthmaR21AI121768 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2016 to 2017
$462k
Regulation of allergen-induced mast cell activation and allergic inflammation through DCIRR21AI137547 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2018 to 2019
$450k
Identification of Candidate Genes for Specific Immune Responsiveness to CockroachR21AI088406 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BARNES, KATHLEEN C, GAO, PEISONG · 2010 to 2011
$449k
Lineage Commitment of Mesenchymal Stem Cell in Allergen-induced Airway RemodelingR21AI109062 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2014 to 2015
$446k
NIAID NIH HHS R21 AI088406NIAID NIH HHS R21 AI109062NIAID NIH HHS R21 AI121768NIAID NIH HHS R21 AI137547NIEHS NIH HHS R01 ES021739
6 · The paper itself

Abstract

backgroundNumbers of mesenchymal stem cells (MSCs) are increased in the airways after allergen challenge. Ras homolog family member A (RhoA)/Rho-associated protein kinase 1 (ROCK) signaling is critical in determining the lineage fate of MSCs in tissue repair/remodeling.

objectivesWe sought to investigate the role of RhoA/ROCK signaling in lineage commitment of MSCs during allergen-induced airway remodeling and delineate the underlying mechanisms.

methodsActive RhoA expression in lung tissues of asthmatic patients and its role in cockroach allergen-induced airway inflammation and remodeling were investigated. RhoA/ROCK signaling-mediated MSC lineage commitment was assessed in an asthma mouse model by using MSC lineage tracing mice (nestin-Cre; ROSA26-EYFP). The role of RhoA/ROCK in MSC lineage commitment was also examined by using MSCs expressing constitutively active RhoA (RhoA-L63) or dominant negative RhoA (RhoA-N19). Downstream RhoA-regulated genes were identified by using the Stem Cell Signaling Array.

resultsLung tissues from asthmatic mice showed increased expression of active RhoA when compared with those from control mice. Inhibition of RhoA/ROCK signaling with fasudil, a RhoA/ROCK inhibitor, reversed established cockroach allergen-induced airway inflammation and remodeling, as assessed based on greater collagen deposition/fibrosis. Furthermore, fasudil inhibited MSC differentiation into fibroblasts/myofibroblasts but promoted MSC differentiation into epithelial cells in asthmatic nestin-Cre; ROSA26-EYFP mice. Consistently, expression of RhoA-L63 facilitated differentiation of MSCs into fibroblasts/myofibroblasts, whereas expression of RhoA-19 switched the differentiation toward epithelial cells. The gene array identified the Wnt signaling effector lymphoid enhancer-binding factor 1 (Lef1) as the most upregulated gene in RhoA-L63-transfected MSCs. Knockdown of Lef1 induced MSC differentiation away from fibroblasts/myofibroblasts but toward epithelial cells.

conclusionsThese findings uncover a previously unrecognized role of RhoA/ROCK signaling in MSC-involved airway repair/remodeling in the setting of asthma.

Indexed as

Airway RemodelingAnimalsAsthmaCell LineageLymphoid Enhancer-Binding Factor 1Mesenchymal Stem CellsMiceMice, Inbred C57BLrhoA GTP-Binding Proteinrho-Associated KinasesSignal TransductionLef1 protein, mouseLymphoid Enhancer-Binding Factor 1rhoA GTP-Binding Proteinrho-Associated KinasesRock1 protein, mouseAsthmacockroach allergenLef1mesenchymal stem cellRas homolog family member A/Rho-associated protein kinase 1

Identifiers

PMID30194990
PMCPMC6401351
OpenAlexW2889807411

What OpenQuestion holds

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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.