Evidence map›Paper›PMID 29940794›Full record

ArticleAutophagy2018

Silica nanoparticles induce autophagosome accumulation via activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes.

Ji Wang, Yang Li, Junchao Duan, Man Yang, Yang Yu, Lin Feng, Xiaozhe Yang, Xianqing Zhou, Zhendong Zhao, Zhiwei Sun

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

  1. Guideline
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  7. Autophagy-Mediated Suppression of Tumor Growth by Food-Grade Lipid Nanoparticles in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  8. Article
  9. Article
  10. Review
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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

10 authors at 2 institutions in 1 country.

Ji Wanga Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Yang Lia Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Junchao Duana Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Man Yanga Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Yang Yua Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Lin Fenga Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Xiaozhe Yanga Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Xianqing Zhoua Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Zhendong Zhaoc MOH Key Laboratory of Systems Biology of Pathogens , Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
Zhiwei Suna Department of Toxicology and Sanitary Chemistry , School of Public Health, Capital Medical University , Beijing , P.R. China.
Capital Medical University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Autophagy dysfunction is a potential toxic effect of nanoparticles. Previous studies have indicated that silica nanoparticles (SiNPs) induce macroautophagy/autophagy dysfunction, while the precise mechanisms remain uncertain. Hence, the present study investigated the molecular mechanisms by which SiNPs enhanced autophagosome synthesis, which then contributed to autophagy dysfunction. First, the effects of SiNPs on autophagy and autophagic flux were verified using transmission electron microscopy, laser scanning confocal microscopy, and western blot assays. Then, the activation of endoplasmic reticular (ER) stress was validated to be through the EIF2AK3 and ATF6 UPR pathways but not the ERN1-XBP1 pathway, along with the upregulation of downstream ATF4 and DDIT3. Thereafter, the ER stress inhibitor 4-phenylbutyrate (4-PBA) was used to verify that SiNP-induced autophagy could be influenced by ER stress. Furthermore, specialized lentiviral shRNA were employed to determine that autophagy was induced via specific activation of the EIF2AK3 and ATF6 UPR pathways. Finally, the 2 autophagic genes LC3B and ATG12 were found to be transcriptionally upregulated by downstream ATF4 and DDIT3 in ER stress, which contributed to the SiNP-enhanced autophagosome synthesis. Taken together, these data suggest that SiNPs induced autophagosome accumulation via the activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes, which offers a new insight into detailed molecular mechanisms underlying SiNP-induced autophagy dysfunction, and specifically how UPR pathways regulate key autophagic genes. This work provides novel evidence for the study of toxic effects and risk assessment of SiNPs.

Indexed as

Unfolded Protein ResponseActivating Transcription Factor 4Activating Transcription Factor 6AutophagosomesAutophagyAutophagy-Related Protein 12Cell LineeIF-2 KinaseEndocytosisEndoplasmic Reticulum StressHepatocytesHumansHydrodynamicsMicrotubule-Associated ProteinsModels, BiologicalNanoparticles4-phenylbutyric acidActivating Transcription Factor 4Activating Transcription Factor 6ATF6 protein, humanAtg12 protein, mouseAutophagy-Related Protein 12Ddit3 protein, mouseEIF2AK3 protein, humaneIF-2 KinaseMap1lc3b protein, mouseMicrotubule-Associated ProteinsPhenylbutyratesSilicon DioxideTranscription Factor CHOPATF6autophagosome accumulationautophagy dysfunctionEIF2AK3ER stresssilica nanoparticles

Identifiers

PMID29940794
PMCPMC6103719
OpenAlexW2810467982

What OpenQuestion holds

Textmetadata
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.