Evidence map›Paper›PMID 34101619›Full record

ArticleJCI insight2021

Type II alveolar epithelial cell-specific loss of RhoA exacerbates allergic airway inflammation through SLC26A4.

Danh C Do, Yan Zhang, Wei Tu, Xinyue Hu, Xiaojun Xiao, Jingsi Chen, Haiping Hao, Zhigang Liu, Jing Li, Shau-Ku Huang and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Repurposing approved drugs as Pendrin (Frontiers in pharmacology · 2026
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  6. Article
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  9. Article
  10. Article
  11. Article
  12. Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.Journal of respiratory biology and translational medicine · 2024
    Article
  13. Article
  14. Review
  15. Effective delivery of miR-511-3p with mannose-decorated exosomes with RNA nanoparticles confers protection against asthma.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Article
  16. Article
  17. Article
  18. 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

12 authors at 5 institutions in 3 countries.

Danh C DoDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yan ZhangDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Wei TuDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Xinyue HuDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Xiaojun XiaoInstitute of Allergy and Immunology, School of Medicine, Shenzhen University, Shenzhen, China.
Jingsi ChenChildren's Hospital, Chongqing Medical University, Chongqing, China.
Haiping HaoJHMI Deep Sequencing and Microarray Core Facility, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Zhigang LiuDepartment of Respirology & Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
Jing LiDepartment of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Shau-Ku HuangDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mei WanDepartment of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Peisong GaoDivision of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Johns Hopkins University · USCentral South University · CNShenzhen University · CNChildren's Hospital of Chongqing Medical University · CNFirst Affiliated Hospital of Guangzhou Medical University · CN

Funding

Environmental Pollutants Potentiate Allergic Inflammation via Functional Axis of Aryl hydrocarbon Receptor, ROS, and CaMKII in AsthmaR01AI141642 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2019 to 2024
$2.9M
Functional role of miR-511-3p in allergic asthma and its underlying mechanismsR01AI153331 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Peisong Gao · 2021 to 2026
$2.7M
Regulation of allergen-induced mast cell activation and allergic inflammation through DCIRR21AI137547 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2018 to 2019
$450k
RhoA signaling controls mesenchymal stem cell lineage commitment via Lef-1 in asthmaR56AI143668 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2019 to 2019
$450k
miR-511-3p, a therapeutic target for allergic asthmaR56ES021739 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI GAO, PEISONG · 2018 to 2018
$150k
NIAID NIH HHS R01 AI141642NIAID NIH HHS R01 AI153331NIAID NIH HHS R21 AI137547NIAID NIH HHS R56 AI143668NIEHS NIH HHS R56 ES021739
6 · The paper itself

Abstract

The small GTPase RhoA and its downstream effectors are critical regulators in the pathophysiological processes of asthma. The underlying mechanism, however, remains undetermined. Here, we generated an asthma mouse model with RhoA-conditional KO mice (Sftpc-cre;RhoAfl/fl) in type II alveolar epithelial cells (AT2) and demonstrated that AT2 cell-specific deletion of RhoA leads to exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, Sftpc-cre;RhoAfl/fl mice showed a significant reduction in Tgf-β1 levels in BALF and lung tissues, and administration of recombinant Tgf-β1 to the mice rescued Tgf-β1 and alleviated the increased allergic airway inflammation observed in Sftpc-cre;RhoAfl/fl mice. Using RNA sequencing technology, we identified Slc26a4 (pendrin), a transmembrane anion exchange, as the most upregulated gene in RhoA-deficient AT2 cells. The upregulation of SLC26A4 was further confirmed in AT2 cells of asthmatic patients and mouse models and in human airway epithelial cells expressing dominant-negative RHOA (RHOA-N19). SLA26A4 was also elevated in serum from asthmatic patients and negatively associated with the percentage of forced expiratory volume in 1 second (FEV1%). Furthermore, SLC26A4 inhibition promoted epithelial TGF-β1 release and attenuated allergic airway inflammation. Our study reveals a RhoA/SLC26A4 axis in AT2 cells that functions as a protective mechanism against allergic airway inflammation.

Indexed as

Alveolar Epithelial CellsAnimalsAsthmaBronchoalveolar Lavage FluidDisease Models, AnimalHumansLungMiceOvalbuminRecombinant ProteinsrhoA GTP-Binding ProteinSulfate TransportersSymptom Flare UpTransforming Growth Factor beta1OvalbuminRecombinant ProteinsrhoA GTP-Binding ProteinRhoA protein, mouseSlc26a4 protein, mouseSulfate TransportersTgfb1 protein, mouseTransforming Growth Factor beta1AllergyAsthmaImmunologyInflammationTh2 response

Identifiers

PMID34101619
PMCPMC8410088
OpenAlexW3168127266

What OpenQuestion holds

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Registered trials

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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.