Evidence map›Paper›PMID 39699913›Full record

ArticleInvestigative ophthalmology & visual science2024

Endoplasmic Reticulum Stress Induces ROS Production and Activates NLRP3 Inflammasome Via the PERK-CHOP Signaling Pathway in Dry Eye Disease.

Zhiwei Zha, Decheng Xiao, Zihao Liu, Fangli Peng, Xunjie Shang, Zhenzhen Sun, Yang Liu, Wei Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–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

19 citing papers in PubMed.

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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

8 authors.

Zhiwei ZhaThe Affiliated Ningbo Eye Hospital of Wenzhou Medical University, Ningbo, Zhejiang, China.
Decheng XiaoState Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zihao LiuState Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Fangli PengState Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Xunjie ShangState Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhenzhen SunState Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yang LiuDepartment of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Wei ChenState Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: The purpose of this study was to investigate the potential roles of endoplasmic reticulum (ER) stress in the development of dry eye disease (DED). Methods: Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, derived from corneal tissues of a dry eye mouse model, was processed using the Seurat R program. The results were validated using a scopolamine-induced dry eye mouse model and a hyperosmotic-induced cell model involving primary human corneal epithelial cells (HCECs) and immortalized human corneal epithelial (HCE-2) cells. The HCE-2 cells were treated with 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) to modulate ER stress. TXNIP and PERK knockdown were performed by siRNA transfection. Immunofluorescence, Western blotting, and real-time PCR were used to assess oxidative stress, ER stress, unfolded protein response (UPR) marker proteins, and TXNIP/NLRP3 axis activation. Results: The analysis of scRNAseq data shows an increase in the ER stress marker GRP78, and the activation of the PERK-CHOP of UPR in DED mouse. These findings were confirmed both in vivo and in vitro. Additionally, HCE-2 cells treated with 4-PBA or TM showed significant effects on the production of reactive oxygen species (ROS) and the activation of the TXNIP/NLRP3-IL1β signaling pathway. Furthermore, siRNA knockdown of PERK or TXNIP, which alleviated the TXNIP/NLRP3-IL1β signaling axis, showed protective effects on HCECs. Conclusions: This study explores the role of ER stress-induced oxidative stress and NLRP3-IL-1β mediated inflammation in DED, and highlights the therapeutic potential of PERK-CHOP axis and TXNIP in the treatment of DED.

Indexed as

Disease Models, AnimalDry Eye SyndromeseIF-2 KinaseEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressInflammasomesMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinReactive Oxygen SpeciesSignal TransductionTranscription Factor CHOPAnimalsBlotting, WesternCarrier ProteinsCells, CulturedEpithelium, CornealCarrier ProteinsDdit3 protein, mouseeIF-2 KinaseEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanHspa5 protein, mouseInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReactive Oxygen SpeciesThioredoxinsTranscription Factor CHOPTxnip protein, mouse

Identifiers

PMID39699913
PMCPMC11668352

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.