Evidence map›Paper›PMID 32724133›Full record

ArticleScientific reports2020

Cigarette smoke induces endoplasmic reticulum stress and suppresses efferocytosis through the activation of RhoA.

Hiroyuki Ito, Yoshiro Yamashita, Takeshi Tanaka, Masahiro Takaki, Minh Nhat Le, Lay-Myint Yoshida, Konosuke Morimoto

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 14% 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, 30 citations in OpenAlex.

  1. Review
  2. Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Efferocytosis in Homeostasis.Advances in experimental medicine and biology · 2025
    Review
  10. Article
  11. Animal models and mechanisms of tobacco smoke-induced chronic obstructive pulmonary disease (COPD).Journal of toxicology and environmental health. Part B, Critical reviews · 2023
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Overexpression of Decay Accelerating Factor Mitigates Fibrotic Responses to Lung Injury.American journal of respiratory cell and molecular biology · 2022
    Article
  18. Article
  19. Article
  20. Autophagy, Unfolded Protein Response and Lung Disease.Current research in cell biology · 2020
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Hiroyuki ItoDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan.
Yoshiro YamashitaDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan.
Takeshi TanakaDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan.
Masahiro TakakiDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan.
Minh Nhat LeDepartment of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Lay-Myint YoshidaDepartment of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Konosuke MorimotoDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan. komorimo@nagasaki-u.ac.jp.
Nagasaki University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Impaired efferocytosis is a key mechanism of inflammatory lung diseases, including chronic obstructive pulmonary disease and cystic fibrosis. Cigarette smoking activates RhoA and impairs efferocytosis in alveolar macrophages, but the mechanism has not been fully elucidated. We investigated the role of endoplasmic reticulum (ER) stress induced by cigarette smoking in the disruption of efferocytosis. Both tunicamycin (10 μg/ml) and thapsigargin (0.1 and 1 μM), which are ER stress inducers, suppressed efferocytosis in J774 cells, and a Rho-associated coiled-coil-forming kinase (ROCK) inhibitor (Y27632) reversed this effect. We validated the effect of tunicamycin on efferocytosis in experiments using RAW264.7 cells. Then, we investigated the role of the unfolded protein response (UPR) in efferocytosis impaired by ER stress. A PERK inhibitor (GSK2606414) restored the efferocytosis that had been impaired by TM, and an eIF2α dephosphorylation inhibitor (salubrinal) suppressed efferocytosis. Cigarette smoke extract (CSE) induced ER stress in J774 macrophages and RhoA activation in J774 cells, and the CSE-induced ROCK activity was successfully reversed by GSK2606414 and tauroursodeoxycholic acid. Finally, we confirmed that ER stress suppresses efferocytosis in murine alveolar macrophages and that GSK2606414 could rescue this process. These data suggest that cigarette smoke-induced ER stress and the UPR play crucial roles in RhoA activation and suppression of efferocytosis in the lung.

Indexed as

Endoplasmic Reticulum StressPhagocytosisAdenineAnimalsCell LineCigarette SmokingeIF-2 KinaseEnzyme ActivationEukaryotic Initiation Factor-2FemaleIndolesMacrophagesMiceMice, Inbred ICRModels, BiologicalrhoA GTP-Binding Protein7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amineAdenineeIF-2 KinaseEukaryotic Initiation Factor-2IndolesrhoA GTP-Binding ProteinRhoA protein, mouserho-Associated KinasesTaurochenodeoxycholic AcidTunicamycinursodoxicoltaurine

Identifiers

PMID32724133
PMCPMC7387437
OpenAlexW3045977206

What OpenQuestion holds

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LicenceCC BY
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.