Evidence map›Paper›PMID 40217328›Full record

ArticleRespiratory research2025

MMP12 deficiency attenuates menthol e-cigarette plus house dust-mite effects on pulmonary iron homeostasis and oxidative stress.

Rakeysha I Pinkston, Matthew Schexnayder, Zakia Perveen, Ingeborg M Langohr, Tomislav Jelesijevic, Arthur L Penn, Alexandra Noël

Abstract read
In one paragraph

Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. 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

7 authors.

Rakeysha I PinkstonDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
Matthew SchexnayderIDEXX Laboratories, Inc., One IDEXX Drive, Westbrook, ME, 04092, USA.
Zakia PerveenDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
Ingeborg M LangohrDepartment of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
Tomislav JelesijevicDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
Arthur L PennDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
Alexandra Noël *Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA. anoel@lsu.edu.

Funding

Cardiopulmonary effects induced by electronic-cigarette and JUUL aerosols in both in vivo and in vitro models.K01HL149053 · NHLBI · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI NOEL, ALEXANDRA · 2020 to 2024
$850k
Louisiana Governor's Biotechnology Initiative GBI-BOR#013National Heart, Lung, and Blood Institute of the National Institutes of Health K01HL149053NHLBI NIH HHS K01 HL149053
6 · The paper itself

Abstract

backgroundLittle is known regarding the pulmonary effects induced by the inhalation of menthol-flavored e-cigarette aerosols on asthma exacerbation, despite the popularity of these devices and flavors among youth and young adults. In the lungs, matrix metalloproteinase 12 (MMP12) expressed and secreted by both alveolar macrophages and bronchial epithelial cells plays an essential role in airway remodeling, a key feature of severe asthma. In this study, we investigated the role of MMP12 in menthol-flavored e-cigarette aerosol exposures plus house-dust mite (HDM)-induced asthmatic responses.

methodsWe exposed wild-type (WT) and MMP12 knockout (KO) juvenile female mice to well-characterized menthol-flavored e-cigarette aerosols followed by either PBS or HDM treatment, and evaluated pulmonary outcomes in terms of iron metabolism, oxidative stress responses and pulmonary inflammation.

resultsWe found high levels of iron in the menthol-flavored e-cigarette aerosol. This correlated with e-cigarette + HDM WT mice exhibiting disruption of pulmonary iron metabolism, suggesting a defense mechanism against iron-mediated toxicity. This was evidenced by altered lung protein concentrations of ferroportin, ferritin, lactoferrin, and transferrin, activation of the antioxidant response element (ARE) pathway and up-regulated expression of NQO1 in e-cigarette + HDM WT mice. Further, despite decreased neutrophilic inflammation, MUC5AC, an oxidative stress inducible mucin, was increased in the e-cigarette + HDM WT mice. In contrast, MMP12 KO mice were protected against iron-induced oxidative stress responses, highlighting a crucial role of MMP12 in this model.

conclusionThese findings revealed in vivo evidence supporting a crucial role for iron metabolism in nicotine salt iron-rich ENDS aerosol toxicity.

Indexed as

AsthmaElectronic Nicotine Delivery SystemsHomeostasisIronLungMatrix Metalloproteinase 12MentholOxidative StressPyroglyphidaeAnimalsFemaleMiceMice, Inbred C57BLMice, KnockoutIronmatrix metallopeptidase 12, mouseMatrix Metalloproteinase 12MentholAsthmaElectronic-cigaretteElectronic nicotine delivery system (ENDS)MMP12Pulmonary iron homeostasis

Identifiers

PMID40217328
PMCPMC11992833

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.