Evidence mapPaperPMID 35906216Full record

ArticleCell death & disease2022

LncRNA ANRIL mediates endothelial dysfunction through BDNF downregulation in chronic kidney disease.

Hong Su, Bing Liu, Huimin Chen, Tingwei Zhang, Tongtong Huang, Yue Liu, Cheng Wang, Qiqi Ma, Qianhui Wang, Zhimei Lv and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.5field-weighted citation impact, top 5% 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, 38 citations in OpenAlex.

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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

11 authors at 2 institutions in 1 country.

Hong Su *Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Bing Liu *Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Huimin ChenDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Tingwei ZhangDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Tongtong HuangDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Yue LiuDepartment of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 250021, Jinan, Shandong, China.
Cheng WangDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Qiqi MaDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Qianhui WangDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China.
Zhimei LvDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China. sdlvzhimei@163.com.ORCID 0000-0003-1634-883X
Rong WangDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China. Wangrong_sd@126.com.
Shandong Provincial Hospital · CNShandong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Endothelial dysfunction is common in patients with chronic kidney disease (CKD), but the mechanism is unknown. In this study, we found that the circulating ANRIL level was increased and correlated with vascular endothelial dysfunction in patients with CKD, also negatively correlated with plasma brain-derived neurotrophic factor (BDNF) concentration. We constructed the ANRIL knockout mice model, and found that ANRIL deficiency reversed the abnormal expression of BDNF, along with endothelial nitric oxide synthase (eNOS), vascular adhesion molecule 1 (VCAM-1) and Von Willebrand factor (vWF). Meanwhile, mitochondrial dynamics-related proteins, Dynamin-related protein 1 (Drp1) and mitofusins (Mfn2) level were also recovered. In addition, in vitro, serum derived from CKD patients and uremia toxins induced abnormal expression of ANRIL. By making use of the gain- and loss-of-function approaches, we observed that ANRIL mediated endothelial dysfunction through BDNF downregulation. To explore the specific mechanism, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) were used to explore the binding of ANRIL to histone methyltransferase Enhancer of zeste homolog 2 (EZH2). Further experiments found increased EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) levels at the BDNF promoter region. Collectively, we demonstrated that ANRIL mediate BDNF transcriptional suppression through recruitment of EZH2 to the BDNF promoter region, then regulated the proteins expression related to endothelial function and mitochondrial dynamics. This study provides new insights for the study of endothelial dysfunction in CKD.

Indexed as

Renal Insufficiency, ChronicRNA, Long NoncodingAnimalsBrain-Derived Neurotrophic FactorDown-RegulationEnhancer of Zeste Homolog 2 ProteinHistone MethyltransferasesMiceBdnf protein, mouseBrain-Derived Neurotrophic FactorEnhancer of Zeste Homolog 2 ProteinHistone MethyltransferasesRNA, Long Noncoding

Identifiers

PMID35906216
PMCPMC9338026
OpenAlexW4288539161

What Socratic 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 Socratic graph.