Evidence map›Paper›PMID 34529881›Full record

ArticleAging cell2021

Activation of angiotensin-converting enzyme 2/angiotensin (1-7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling.

Ruili Dang, Mengqi Yang, Changmeng Cui, Changshui Wang, Wenyuan Zhang, Chunmei Geng, Wenxiu Han, Pei Jiang

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

40 citing papers in PubMed, 65 citations in OpenAlex.

  1. Imbalance of renin-angiotensin system in calcium oxalate crystals-induced renal oxidative stress and autophagy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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  5. Ang II-mediated effects on BBB integrity in psychiatric and neurological disorders.Progress in neuro-psychopharmacology & biological psychiatry · 2026
    Review
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  9. Activation of Hippocampal ACE2 Prevents the Dysbiosis-induced Depression-like Behavior in Mice by Enhanced Neurogenesis and Neuroprotection via Mas Receptor.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
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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 at 3 institutions in 1 country.

Ruili DangInstitute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China.
Mengqi YangInstitute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China.
Changmeng CuiDepartment of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, China.
Changshui WangDepartment of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, China.
Wenyuan ZhangDepartment of Pharmacy, Zhongshan Affiliated Hospital of Zhongshan University, Zhongshan, China.
Chunmei GengInstitute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China.
Wenxiu HanInstitute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China.
Pei JiangInstitute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China.ORCID 0000-0002-8360-7427
Jining First People's Hospital · CNAffiliated Hospital of Jining Medical University · CNZhongshan Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Brain renin-angiotensin (Ang) system (RAS) is implicated in neuroinflammation, a major characteristic of aging process. Angiotensin (Ang) II, produced by angiotensin-converting enzyme (ACE), activates immune system via angiotensin type 1 receptor (AT1), whereas Ang(1-7), generated by ACE2, binds with Mas receptor (MasR) to restrain excessive inflammatory response. Therefore, the present study aims to explore the relationship between RAS and neuroinflammation. We found that repeated lipopolysaccharide (LPS) treatment shifted the balance between ACE/Ang II/AT1 and ACE2/Ang(1-7)/MasR axis to the deleterious side and treatment with either MasR agonist, AVE0991 (AVE) or ACE2 activator, diminazene aceturate, exhibited strong neuroprotective actions. Mechanically, activation of ACE2/Ang(1-7)/MasR axis triggered the Forkhead box class O1 (FOXO1)-autophagy pathway and induced superoxide dismutase (SOD) and catalase (CAT), the FOXO1-targeted antioxidant enzymes. Meanwhile, knockdown of MasR or FOXO1 in BV2 cells, or using the selective FOXO1 inhibitor, AS1842856, in animals, suppressed FOXO1 translocation and compromised the autophagic process induced by MasR activation. We further used chloroquine (CQ) to block autophagy and showed that suppressing either FOXO1 or autophagy abrogated the anti-inflammatory action of AVE. Likewise, Ang(1-7) also induced FOXO1 signaling and autophagic flux following LPS treatment in BV2 cells. Cotreatment with AS1842856 or CQ all led to autophagic inhibition and thereby abolished Ang(1-7)-induced remission on NLRP3 inflammasome activation caused by LPS exposure, shifting the microglial polarization from M1 to M2 phenotype. Collectively, these results firstly illustrated the mechanism of ACE2/Ang(1-7)/MasR axis in neuroinflammation, strongly indicating the involvement of FOXO1-mediated autophagy in the neuroimmune-modulating effects triggered by MasR activation.

Indexed as

Angiotensin-Converting Enzyme 2Angiotensin IAnimalsAutophagyHumansMiceMicrogliaNeuroinflammatory DiseasesPeptide FragmentsSignal TransductionTransfectionAngiotensin-Converting Enzyme 2Angiotensin Iangiotensin I (1-7)Peptide FragmentsautophagyFOXO1neuroinflammationrenin-angiotensin system

Identifiers

PMID34529881
PMCPMC8520723
OpenAlexW3200336280

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.