Evidence map›Paper›PMID 31924219›Full record

ArticleJournal of neuroinflammation2020

HMGB1/RAGE axis mediates stress-induced RVLM neuroinflammation in mice via impairing mitophagy flux in microglia.

Shutian Zhang, Li Hu, Jialun Jiang, Hongji Li, Qin Wu, Kokwin Ooi, Jijiang Wang, Yi Feng, Danian Zhu, Chunmei Xia

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
13.3field-weighted citation impact, top 1% 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

94 citing papers in PubMed, 166 citations in OpenAlex.

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34 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 at 3 institutions in 1 country.

Shutian ZhangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China.
Li HuLaboratory of Neuropharmacology and Neurotoxicology, Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, People's Republic of China.
Jialun JiangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China.
Hongji LiDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China.
Qin WuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China.
Kokwin OoiDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China.
Jijiang WangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China.
Yi FengDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China.
Danian ZhuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China.
Chunmei XiaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130, Dongan Road, Shanghai, 200032, People's Republic of China. cmxia@fudan.edu.cn.ORCID http://orcid.org/0000-0001-9845-9685
Fudan University · CNShanghai Medical College of Fudan University · CNShanghai University · CN

Funding

Chinese National Natural Science Foundation 81770423
6 · The paper itself

Abstract

backgroundMicroglial mediated neuroinflammation in the rostral ventrolateral medulla (RVLM) plays roles in the etiology of stress-induced hypertension (SIH). It was reported that autophagy influenced inflammation via immunophenotypic switching of microglia. High-mobility group box 1 (HMGB1) acts as a regulator of autophagy and initiates the production of proinflammatory cytokines (PICs), but the underlying mechanisms remain unclear.

methodsThe stressed mice were subjected to intermittent electric foot shocks plus noises administered for 2 h twice daily for 15 consecutive days. In mice, blood pressure (BP) and renal sympathetic nerve activity (RSNA) were monitored by noninvasive tail-cuff method and platinum-iridium electrodes placed respectively. Microinjection of siRNA-HMGB1 (siHMGB1) into the RVLM of mice to study the effect of HMGB1 on microglia M1 activation was done. mRFP-GFP-tandem fluorescent LC3 (tf-LC3) vectors were transfected into the RVLM to evaluate the process of autolysosome formation/autophagy flux. The expression of RAB7, lysosomal-associated membrane protein 1 (LAMP1), and lysosomal pH change were used to evaluate lysosomal function in microglia. Mitophagy was identified by transmission electron microscopic observation or by checking LC3 and MitoTracker colocalization under a confocal microscope.

resultsWe showed chronic stress increased cytoplasmic translocations of HMGB1 and upregulation of its receptor RAGE expression in microglia. The mitochondria injury, oxidative stress, and M1 polarization were attenuated in the RVLM of stressed Cre-CX3CR1/RAGE

conclusionsCollectively, we demonstrated that inhibition of the HMGB1/RAGE axis activation led to increased stress-induced mitophagy flux, hence reducing the activity of microglia-mediated neuroinflammation and consequently reduced the sympathetic vasoconstriction drive in the RVLM.

Indexed as

AnimalsHMGB1 ProteinHypertensionInflammationMedulla OblongataMiceMice, Inbred C57BLMicrogliaMitophagyPsychological DistressReceptor for Advanced Glycation End ProductsSignal TransductionStress, PsychologicalAger protein, mouseHMGB1 ProteinHMGB1 protein, mouseReceptor for Advanced Glycation End ProductsAutophagyHigh-mobility group box 1HypertensionMicrogliaMitochondriaNeuroinflammationRAGEStress

Identifiers

PMID31924219
PMCPMC6953162
OpenAlexW2998866195

What OpenQuestion holds

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LicenceCC BY
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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.