Evidence map›Paper›PMID 30170968›Full record

ArticleEBioMedicine2018

Boosting mTOR-dependent autophagy via upstream TLR4-MyD88-MAPK signalling and downstream NF-κB pathway quenches intestinal inflammation and oxidative stress injury.

Mingxia Zhou, Weimin Xu, Jiazheng Wang, Junkai Yan, Yingying Shi, Cong Zhang, Wensong Ge, Jin Wu, Peng Du, Yingwei Chen

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PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
212citing papers in PubMed, 2 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

212 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  11. Appendix in ulcerative colitis pathogenesis and therapy: An updated narrative review.World journal of gastrointestinal pathophysiology · 2026
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152 more citing papers are in PubMed but not listed here.

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.

Mingxia ZhouDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: mingxiazhou@sjtu.edu.cn.
Weimin XuDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: xuweimin@sjtu.edu.cn.
Jiazheng WangDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: wangjiazheng1991@sjtu.edu.cn.
Junkai YanShanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: yanjunkai2015@sjtu.edu.cn.
Yingying ShiDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: syy_0802@sjtu.edu.cn.
Cong ZhangDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: zhang-cong@alumni.sjtu.edu.cn.
Wensong GeDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: gewensong@xinhuamed.com.cn.
Jin WuShanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: wujin51@yahoo.com.
Peng DuDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: dupeng@xinhuamed.com.cn.
Yingwei ChenDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: chenyingwei@xinhuamed.com.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsDefective autophagy has been proposed as an important event in a growing number of autoimmune and inflammatory diseases such as rheumatoid arthritis and lupus. However, the precise role of mechanistic target of rapamycin (mTOR)-dependent autophagy and its underlying regulatory mechanisms in the intestinal epithelium in response to inflammation and oxidative stress remain poorly understood.

methodsThe levels of p-mTOR, LC3B, p62 and autophagy in mice and LPS-treated cells were examined by immunoblotting, immunohistochemistry, confocal microscopy and transmission electron microscopy (TEM). We evaluated the expression of IL-1β, IL-8, TNF-α, MDA, SOD and T-AOC by quantitative real time-polymerase chain reaction (qRT-PCR) and commercially available kits after silencing of mTOR and ATG5. In vivo modulation of mTOR and autophagy was achieved by using AZD8055, rapamycin and 3-methyladenine. Finally, to verify the involvement of TLR4 signalling and the NF-κB pathway in cells and active ulcerative colitis (UC) patients, immunofluorescence, qRT-PCR, immunoblotting and TEM were performed to determine TLR4 signalling relevance to autophagy and inflammation.

resultsThe mTOR-dependent autophagic flux impairment in a murine model of colitis, human intestinal epithelial cells and active UC patients is probably regulated by TLR4-MyD88-MAPK signalling and the NF-κB pathway. Silencing mTOR remarkably attenuated, whereas inhibiting ATG5 aggravated, LPS-induced inflammation and oxidative injury. Pharmacological administration of mTOR inhibitors and autophagy stimulators markedly ameliorated experimental colitis and oxidative stress in vivo.

conclusionsOur findings not only shed light on the regulatory mechanism of mTOR-dependent autophagy, but also provided potential therapeutic targets for intestinal inflammatory diseases such as refractory inflammatory bowel disease.

Indexed as

AutophagyOxidative StressAnimalsAutophagy-Related Protein 5Cell Line, TumorColitisColitis, UlcerativeFemaleGene SilencingHumansInflammationIntestinesLipopolysaccharidesMAP Kinase Signaling SystemMice, Inbred BALB CMyeloid Differentiation Factor 88ATG5 protein, humanAutophagy-Related Protein 5LipopolysaccharidesMyeloid Differentiation Factor 88NF-kappa BToll-Like Receptor 4TOR Serine-Threonine KinasesAutophagyInflammationmTOROxidative stress

Identifiers

PMID30170968
PMCPMC6161481

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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.