Evidence map›Paper›PMID 27785530›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2017

Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline.

Wei Chen, Minjie Zhao, Shuzhi Zhao, Qianyi Lu, Lisha Ni, Chen Zou, Li Lu, Xun Xu, Huaijin Guan, Zhi Zheng and 1 more

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
6.3field-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

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.

  1. Pooled it
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  16. Dopamine: A New Player in the Pathogenesis of Diabetic Retinopathy?International journal of molecular sciences · 2024
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  19. Article
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35 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

11 authors at 4 institutions in 1 country.

Wei ChenDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
Minjie ZhaoDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
Shuzhi ZhaoDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
Qianyi LuDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
Lisha NiDepartment of Ophthalmology, Lishui People's Hospital, Lishui, 323000, Zhejiang, China.
Chen ZouDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
Li LuDepartment of Ophthalmology, Anhui Provincial Hospital, Hefei, China.
Xun XuDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
Huaijin GuanDepartment of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Zhi ZhengDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China. zzheng88@sjtu.edu.cn.
Qinghua QiuDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China. qinghuaqiu@163.com.
Shanghai First People's Hospital · CNAffiliated Hospital of Nantong University · CNAnhui Provincial Hospital · CNLishui City People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

OBJECTIVE AND

designChronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR.

methodsDiabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference.

resultsIn high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1β and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS-TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis.

conclusionsTogether, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.

Indexed as

AnimalsAnti-Inflammatory AgentsApoptosisCapillary PermeabilityCarrier ProteinsCaspase 1Caspase 3Cell Cycle ProteinsCells, CulturedDiabetes Mellitus, ExperimentalDiabetic RetinopathyEndothelial CellsGlucoseHumansInflammasomesInflammationAnti-Inflammatory AgentsCarrier ProteinsCaspase 1Caspase 3Cell Cycle ProteinsGlucoseInflammasomesInterleukin-18Interleukin-1betaMinocyclineNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratReactive Oxygen SpeciesRNA, Small InterferingTXNIP protein, ratDiabetic retinopathyMinocyclineNLRP3 inflammasome

Identifiers

PMID27785530
OpenAlexW2542571717

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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.