Evidence map›Paper›PMID 36803854›Full record

ArticleJournal of biomedical science2023

ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking.

Chu-Hsuan Chiu, Chin-Feng Hsuan, Shih-Hua Lin, Yi-Jen Hung, Chii-Min Hwu, Siow-Wey Hee, Shu-Wha Lin, Sitt-Wai Fong, Patrick Ching-Ho Hsieh, Wei-Shun Yang and 10 more

Open access · diamondAbstract read
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Article in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

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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.

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

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4 · The record

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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

20 authors at 6 institutions in 2 countries.

Chu-Hsuan ChiuGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, 100, Taiwan.
Chin-Feng HsuanDivision of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, 824410, Taiwan.
Shih-Hua LinGraduate Institute of Medical Science, National Defense Medical Center, Taipei, 114, Taiwan.
Yi-Jen HungDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 100, Taiwan.
Chii-Min HwuFaculty of Medicine, National Yang-Ming University School of Medicine, Taipei, 112, Taiwan.
Siow-Wey HeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
Shu-Wha LinDivision of Genomic Medicine, Research Center for Medical Excellence, Transgenic Mouse Models Core, National Taiwan University, Taipei, 100, Taiwan.
Sitt-Wai FongInstitute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
Patrick Ching-Ho HsiehInstitute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
Wei-Shun YangGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, 100, Taiwan.
Wei-Chou LinDepartment of Pathology, National Taiwan University Hospital, Taipei, 100, Taiwan.
Hsiao-Lin LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
Meng-Lun HsiehDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
Wen-Yi LiDivision of Nephrology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, 640, Taiwan.
Jou-Wei LinDivision of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, 640, Taiwan.
Chih-Neng HsuDivision of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, 640, Taiwan.
Vin-Cent WuDivision of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
Gwo-Tsann ChuangGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, 100, Taiwan.
Yi-Cheng ChangGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, 100, Taiwan. b83401040@gmail.com.
Lee-Ming ChuangDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan. leeming@ntu.edu.tw.ORCID http://orcid.org/0000-0003-0978-2662
National Taiwan University · TWNational Taiwan University Hospital · TWInstitute of Biomedical Sciences, Academia Sinica · TWTri-Service General Hospital · TWE-Da Hospital · TWUniversity of Florida · US

Funding

he Joint Research Project of Far Eastern Memorial Hospital and National Taiwan University Hospital 109 FTN06Innovative Research Grant of the National Health Research Institute NHRI-EX106-10532S1Institute of Biomedical Sciences, Academia Sinica AS-TM-109-01-03intramural grant of National Taiwan University Hospital NTUH 109-004519National Taiwan University Hospital Yunlin Branch NTHHYL.110.X017National Taiwan University Hospital Yunlin Branch NTUHYL107.S004National Taiwan University Hospital Yunlin Branch NTUHYL.107.S013National Taiwan University Hospital Yunlin Branch NTUHYL. X019
6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown.

methodsTo identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model.

resultsIn the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion.

conclusionsRRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.

Indexed as

Carrier ProteinsHyperkalemiaHypertensionHypoaldosteronismAldosteroneAluminum OxideAnimalsBlood PressureGenome-Wide Association StudyHomeostasisHumansMicePotassiumReninAldosteroneAluminum OxideCarrier ProteinsPotassiumReninRRBP1 protein, humanArrhythmiaBlood pressureCardiovascular diseaseHyperkalemiaHyporeninemic hypoaldosteronismRenin–angiotensin–aldosterone systemRRBP1

Identifiers

PMID36803854
PMCPMC9940419
OpenAlexW4321351629

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LicenceCC BY
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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.