Evidence map›Paper›PMID 37869777›Full record

ArticleCNS neuroscience & therapeutics2024

Circular RNA PTP4A2 regulates microglial polarization through STAT3 to promote neuroinflammation in ischemic stroke.

Xingzhi Wang, Shenyang Zhang, Bingchen Lv, Hao Chen, Wei Zhang, Liguo Dong, Lei Bao, Miao Wang, Yan Wang, Wenqi Mao and 6 more

Open access · goldAbstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

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  17. Minocycline AmelioratesBrain sciences · 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

16 authors at 2 institutions in 1 country.

Xingzhi WangDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.ORCID 0000-0001-9248-3510
Shenyang ZhangDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Bingchen LvDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Hao ChenDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Wei ZhangDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Liguo DongDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Lei BaoDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Miao WangDepartment of Geriatrics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Yan WangDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Wenqi MaoDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Likun CuiDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Ye PangDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Fei WangDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Fuling YanDepartment of Neurology, Affiliated to ZhongDa Hospital of Southeast University, Nanjing, China.
Zuohui ZhangDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Guiyun CuiDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.ORCID 0000-0002-8467-5798
Xuzhou Medical College · CNZhongda Hospital Southeast University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveMicroglial polarization plays a critical role in neuroinflammation and may be a potential therapeutic target for ischemic stroke. This study was to explore the role and underlying molecular mechanism of Circular RNA PTP4A2 (circPTP4A2) in microglial polarization after ischemic stroke.

methodsC57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO), while primary mouse microglia and BV2 microglial cells experienced oxygen glucose deprivation/reperfusion (OGD/R) to mimic ischemic conditions. CircPTP4A2 shRNA lentivirus and Colivelin were used to knock down circPTP4A2 and upregulate signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. Microglial polarization was assessed using immunofluorescence staining and Western blot. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were applied to detect the binding between circPTP4A2 and STAT3.

resultsThe levels of circPTP4A2 were significantly increased in plasma and peri-infarct cortex in tMCAO mice. CircPTP4A2 knockdown reduced infarct volume, increased cortical cerebral blood flow (CBF), and attenuated neurological deficits. It also decreased pro-inflammatory factors levels in peri-infarct cortex and plasma, and increased anti-inflammatory factors concentrations 24 h post-stroke. In addition, circPTP4A2 knockdown suppressed M1 microglial polarization and promoted M2 microglial polarization in both tMCAO mice and OGD/R-induced BV2 microglial cells. Moreover, circPTP4A2 knockdown inhibited the phosphorylation of STAT3 induced by oxygen-glucose deprivation. In contrast, increased phosphorylation of STAT3 partly counteracted the effects of circPTP4A2 knockdown. RNA pull-down and RIP assays further certified the binding between circPTP4A2 and STAT3.

conclusionThese results revealed regulatory mechanisms of circPTP4A2 that stimulated neuroinflammation by driving STAT3-dependent microglial polarization in ischemic brain injury. CircPTP4A2 knockdown reduced cerebral ischemic injury and promoted microglial M2 polarization, which could be a novel therapeutic target for ischemic stroke.

Indexed as

Brain InjuriesBrain IschemiaIschemic StrokeRNA, CircularAnimalsGlucoseImmediate-Early ProteinsInfarction, Middle Cerebral ArteryMiceMice, Inbred C57BLMicrogliaNeuroinflammatory DiseasesOxygenProtein Tyrosine PhosphatasesSTAT3 Transcription FactorGlucoseImmediate-Early ProteinsOxygenProtein Tyrosine PhosphatasesPtp4a2 protein, mouseRNA, CircularSTAT3 Transcription FactorcircPTP4A2inflammationischemic strokemicrogliaSTAT3

Identifiers

PMID37869777
PMCPMC11017462
OpenAlexW4387865801

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.