Traffic-related ultrafine particles influence gene regulation in olfactory mucosa cells altering PI3K/AKT signaling
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00619631" target="_blank" >RIV/68378041:_____/25:00619631 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0160412025002351?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0160412025002351?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.envint.2025.109484" target="_blank" >10.1016/j.envint.2025.109484</a>
Alternative languages
Result language
angličtina
Original language name
Traffic-related ultrafine particles influence gene regulation in olfactory mucosa cells altering PI3K/AKT signaling
Original language description
Traffic-related ultrafine particles (UFPs) are an emerging health concern affecting the brain and increasing the risk of Alzheimer's disease (AD). PI3K/AKT signaling is known to contribute to neuronal survival and to be altered in AD. The nasal olfactory mucosa (OM) is a sensory tissue exposed directly to ambient air, and a starting point for olfactory neural circuits towards the brain. Evidence of air pollution-induced transcriptional regulation via microRNAs (miRNA) and DNA methylation (DNAmet) is accumulating and air pollutant-mediated disturbances in PI3K/AKT signaling have been reported. By utilizing a highly translational human-based in vitro model of OM, we aimed to investigate possible gene regulatory mechanisms in PI3K/AKT signaling induced by UFPs, and to compare the responses between cognitively healthy and individuals with AD. miRNA expression was analyzed using next-generation sequencing (NGS) and chip-based methylation analysis was performed to detect differentially methylated loci (DML). These data were combined with previously published transcriptomics analysis (mRNA) to construct an mRNA-miRNA-DNAmet-integrative network. Protein level changes were studied by immunoassays. We observed UFP-induced reductions in viability and increases in oxidative stress and DNA damage without eminent cell death. Integrative network analysis revealed multiple connections of miRNAs to differentially expressed genes in the PI3K/AKT pathway, and effects were most prominent in AD cells. Similarly, in AD cells DML were identified in transcription factor and apoptosis genes, downstream of PI3K/AKT signaling. Conclusively, traffic-related UFPs influence gene regulation of PI3K/AKT signaling to modulate OM cell survival, with existing AD pathology resulting in heightened vulnerability to UFP effects.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30304 - Public and environmental health
Result continuities
Project
<a href="/en/project/LM2023066" target="_blank" >LM2023066: Nanomaterials and Nanotechnologies for Environment Protection and Sustainable Future</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Environment International
ISSN
0160-4120
e-ISSN
1873-6750
Volume of the periodical
199
Issue of the periodical within the volume
May
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
109484
UT code for WoS article
001479532500001
EID of the result in the Scopus database
2-s2.0-105003211254