ArticleJournal of nanobiotechnology2020
p62/SQSTM1 accumulation due to degradation inhibition and transcriptional activation plays a critical role in silica nanoparticle-induced airway inflammation via NF-κB activation.
Article in Journal of nanobiotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Dual Roles of Autophagy in Endometrial Fibrosis and Its Implications in Age-Related Reproductive Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Green-Synthesis of Cerium Oxide Nanoparticles using Ferula Latisecta Extract: Characterization, Oxidative Stress, Autophagy, and Apoptosis Signaling in Human Colorectal Cancer Cells.Applied biochemistry and biotechnology · 2026Article
- RIPK3/SQSTM1-Mediated Necroptosis Activates the NLRP3 Inflammasome in Dry Eye Disease.Investigative ophthalmology & visual science · 2026Article
- Gap junction protein connexin 36 proteostatic mechanisms in photoreceptor cells subjected to excitotoxic stress.Acta biochimica Polonica · 2026Article
- Gastrodin alleviates cardiomyocyte senescence by regulating autophagy through the AMPK/mTOR/4EBP1 pathway.Frontiers in pharmacology · 2026Article
- Comparative Analysis of the Tolerance of Young and Old Kidneys to Injury in a Rat Model of Reversible Ureteral Obstruction.Antioxidants (Basel, Switzerland) · 2025Article
- Neodymium-doped mesoporous silica nanoparticles promote bone regeneration via autophagy-mediated macrophage immunomodulation.Materials today. Bio · 2025Article
- Antae-eum, a herbal formula, relieves LPS-induced inflammatory response in macrophages via suppression of autophagic flux.Scientific reports · 2025Article
- Targeting Autophagy for Pituitary Tumors.Cancers · 2025Review
- Association between SQSTM1 dysregulation and risk in alopecia areata: a Mendelian randomization study.Frontiers in immunology · 2025Article
- Comparative effects of 3,5-diiodo-L-thyronine and 3,5,3'-triiodo-L-thyronine on mitochondrial damage and cGAS/STING-driven inflammation in liver of hypothyroid rats.Frontiers in endocrinology · 2024Article
- Unexpected Inhibitory Role of Silica Nanoparticles on Lung Cancer Development by Promoting M1 Polarization of Macrophages.International journal of nanomedicine · 2024Article
- The Genetic and Epigenetic Toxicity of Silica Nanoparticles: An Updated Review.International journal of nanomedicine · 2024Review
- Article
- Autophagy-associated immune dysregulation and hyperplasia in a patient with compound heterozygous mutations inAutophagy · 2023Article
- 6,6'-((Methylazanedyl)bis(methylene))bis(2,4-dimethylphenol) Induces Autophagic Associated Cell Death through mTOR-Mediated Autophagy in Lung Cancer.Molecules (Basel, Switzerland) · 2022Article
- Article
- Evaluation of histopathological changes and exosomal biogenesis in pulmonary tissue of diabetic rats.Veterinary research forum : an international quarterly journal · 2022Article
- Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach.Molecular medicine (Cambridge, Mass.) · 2021Article
- Micro- and Nanosized Substances Cause Different Autophagy-Related Responses.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMost nanoparticles (NPs) reportedly block autophagic flux, thereby upregulating p62/SQSTM1 through degradation inhibition. p62 also acts as a multifunctional scaffold protein with multiple domains, and is involved in various cellular processes. However, the autophagy substrate-independent role of p62 and its regulation at the transcriptional level upon NPs exposure remain unclear.
resultsIn this work, we exposed BEAS-2b cells and mice to silica nanoparticles (SiNPs), and found that SiNPs increased p62 protein levels in vivo and vitro. Then, we further explored the role and mechanism of SiNPs-stimulated p62 in vitro, and found that p62 degradation was inhibited due to autophagic flux blockade. Mechanistically, SiNPs blocked autophagic flux through impairment of lysosomal capacity rather than defective autophagosome fusion with lysosomes. Moreover, SiNPs stimulated translocation of NF-E2-related factor 2 (Nrf2) to the nucleus from the cytoplasm, which upregulated p62 transcriptional activation through direct binding of Nrf2 to the p62 promoter. Nrf2 siRNA dramatically reduced both the mRNA and protein levels of p62. These two mechanisms led to p62 protein accumulation, thus increasing interleukin (IL)-1 and IL-6 expression. SiNPs activated nuclear factor kappa B (NF-κB), and this effect could be alleviated by p62 knockdown.
conclusionSiNPs caused accumulation of p62 through both pre- and post-translational mechanisms, resulting in airway inflammation. These findings improve our understanding of SiNP-induced pulmonary damage and the molecular targets available to mitigate it.
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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.