Evidence map›Paper›PMID 39227917›Full record

ArticleJournal of translational medicine2024

BRCC36 regulates β-catenin ubiquitination to alleviate vascular calcification in chronic kidney disease.

Yalan Li, Xiaoyue Chen, Yiqing Xiong, Xueqiang Xu, Caidie Xie, Min Min, Dongmei Liang, Cheng Chen, Huijuan Mao

Abstract read
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. 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.

Yalan Li *Department of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China.
Xiaoyue Chen *Department of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China.
Yiqing Xiong *Department of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China.
Xueqiang XuDepartment of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China.
Caidie XieDepartment of General Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, #1-1 Zhongfu Road, Nanjing, 210003, China.
Min MinDepartment of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China.
Dongmei LiangDepartment of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China.
Cheng ChenDepartment of Medical Science, Yangzhou Polytechnic College, #458 West Wenchang Road, Yangzhou, 225009, China. yishixingtaicc@163.com.
Huijuan MaoDepartment of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China. maohuijuan72@njmu.edu.cn.ORCID 0000-0001-7410-1486

Funding

National Natural Science Foundation of China 82070246National Natural Science Foundation of China 82151320
6 · The paper itself

Abstract

backgroundThe prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC.

methodsThe association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/β-catenin pathway.

resultsBRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/β-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/β-catenin pathway by decreasing the K63-linked ubiquitination of β-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression.

conclusionsOur research results emphasize the critical role of the BRCC36-β-catenin axis in VC, suggesting that BRCC36 or β-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients.

Indexed as

beta CateninMice, Inbred C57BLRenal Insufficiency, ChronicUbiquitinationVascular CalcificationWnt Signaling PathwayAnimalsCell DifferentiationDeubiquitinating EnzymesHumansMaleMiceMiddle AgedMuscle, Smooth, VascularMyocytes, Smooth MuscleOsteogenesisbeta CateninBRCC3 protein, humanBRCC3 protein, mouseCTNNB1 protein, humanCTNNB1 protein, mouseDeubiquitinating EnzymesBRCC36Chronic kidney diseaseUbiquitin‒proteasome degradationVascular calcificationβ-catenin

Identifiers

PMID39227917
PMCPMC11373267

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.