Evidence map›Paper›PMID 39777866›Full record

ArticleCNS neuroscience & therapeutics2025

Rnf40 Exacerbates Hypertension-Induced Cerebrovascular Endothelial Barrier Dysfunction by Ubiquitination and Degradation of Parkin.

Chengkun Kou, Xu Zhao, Xin Fan, Runmin Sun, Wenting Wang, Miaomiao Qi, Lulu Zhu, Xin Lin, Jing Yu

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

9 authors.

Chengkun KouHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Xu ZhaoHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Xin FanHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Runmin SunHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Wenting WangHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Miaomiao QiHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Lulu ZhuHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Xin LinHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Jing YuHypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.ORCID 0000-0002-4164-764X

Funding

Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital CY2021-MS-A13Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital CY2021-QN-A11Gansu Province Education Science and Technology Innovation Project 2022-B042Gansu Province Health Research Project GSWSKY2017-02International Science and Technology Cooperation Base PR0124002National Natural Science Foundation of China NSFC 81960086National Natural Science Foundation of China NSFC 82160089Special Fund Project for Doctoral Training of Lanzhou University Second Hospital YJS-BD-24
6 · The paper itself

Abstract

aimsWe aimed to investigate the role of Rnf40 in hypertension-induced cerebrovascular endothelial barrier dysfunction and cognitive impairment.

methodsWe employed microarray data analysis and integrated bioinformatics databases to identify a novel E3 ligase, Rnf40, that targets Parkin. To understand the role of RNF40 in hypertension-induced cerebrovascular endothelial cell damage, we used pAAV-hFLT1-MCS-EGFP-3×Flag-mir30shRnf40 to establish an Rnf40-deficient model in spontaneously hypertensive rats (SHRs). We also evaluated the cerebrovascular endothelial barrier function, cerebral blood flow, and cognitive performance.

resultsWe observed reduced mitophagy in cerebrovascular endothelial cells of SHRs compared with that in Wistar-Kyoto rats. Rnf40 facilitated K48-linked polyubiquitination and degradation of Parkin, thereby inhibiting mitophagy. In the Rnf40-deficient SHR model, knocking down Rnf40 restored mitophagy in cerebrovascular endothelial cells. Additionally, levels of tight junction proteins and cerebrovascular endothelial barrier function improved following Rnf40 downregulation. Rnf40 depletion also improved global cognitive performance and restored cerebral blood flow in SHRs.

conclusionOur findings suggest that increased Rnf40 levels exacerbate hypertension-induced cerebrovascular endothelial barrier dysfunction by ubiquitinating Parkin.

Indexed as

HypertensionRats, Inbred SHRRats, Inbred WKYUbiquitinationUbiquitin-Protein LigasesAnimalsBlood-Brain BarrierEndothelial CellsHumansMaleMitophagyRatsparkin proteinUbiquitin-Protein Ligasescerebrovascular endothelial barriercognitionendothelial cellhypertensionmitophagyRnf40

Identifiers

PMID39777866
PMCPMC11707429

What OpenQuestion holds

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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.