Evidence map›Paper›PMID 26582775›Full record

ArticleCirculation research2016

Identification of the (Pro)renin Receptor as a Novel Regulator of Low-Density Lipoprotein Metabolism.

Xifeng Lu, Marcel E Meima, Jessica K Nelson, Vincenzo Sorrentino, Anke Loregger, Saskia Scheij, Dick H W Dekkers, Monique T Mulder, Jeroen A A Demmers, Geesje M-Dallinga-Thie and 2 more

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In one paragraph

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

20 citing papers in PubMed, 47 citations in OpenAlex.

  1. Trial
  2. Review
  3. Vacuolar HJournal of cellular physiology · 2025
    Article
  4. Review
  5. Article
  6. Review
  7. The V-ATPaseInternational journal of molecular sciences · 2021
    Review
  8. The prorenin receptor and its soluble form contribute to lipid homeostasis.American journal of physiology. Endocrinology and metabolism · 2021
    Article
  9. Immunohistochemistry for (Pro)renin Receptor in Humans.International journal of endocrinology · 2021
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. The (pro)renin receptor in health and disease.Nature reviews. Nephrology · 2019
    Review
  15. Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Xifeng LuFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Marcel E MeimaFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Jessica K NelsonFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Vincenzo SorrentinoFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Anke LoreggerFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Saskia ScheijFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Dick H W DekkersFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Monique T MulderFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Jeroen A A DemmersFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Geesje M-Dallinga-ThieFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands.
Noam ZelcerFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands. a.danser@erasmusmc.nl n.zelcer@amc.uva.nl.
A H Jan DanserFrom the Astra Zeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Medical Center, Shenzhen University, Shenzhen, China (X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (X.L., M.E.M., M.T.M., A.H.J.D.) and Proteomics Center (D.H.W.D., J.A.A.D.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Medical Biochemistry (X.L., J.K.N., V.S., A.L., S.S., N.Z.) and Laboratory of Experimental Vascular Medicine (G.M.D-.T.), Academic Medical Center, Amsterdam, The Netherlands. a.danser@erasmusmc.nl n.zelcer@amc.uva.nl.
Shenzhen University · CNErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleThe (pro)renin receptor ([P]RR) interacts with (pro)renin at concentrations that are >1000× higher than observed under (patho)physiological conditions. Recent studies have identified renin-angiotensin system-independent functions for (P)RR related to its association with the vacuolar H(+)-ATPase.

objectiveTo uncover renin-angiotensin system-independent functions of the (P)RR. METHODS AND

resultsWe used a proteomics-based approach to purify and identify (P)RR-interacting proteins. This resulted in identification of sortilin-1 (SORT1) as a high-confidence (P)RR-interacting protein, a finding which was confirmed by coimmunoprecipitation of endogenous (P)RR and SORT1. Functionally, silencing (P)RR expression in hepatocytes decreased SORT1 and low-density lipoprotein (LDL) receptor protein abundance and, as a consequence, resulted in severely attenuated cellular LDL uptake. In contrast to LDL, endocytosis of epidermal growth factor or transferrin remained unaffected by silencing of the (P)RR. Importantly, reduction of LDL receptor and SORT1 protein abundance occurred in the absence of changes in their corresponding transcript level. Consistent with a post-transcriptional event, degradation of the LDL receptor induced by (P)RR silencing could be reversed by lysosomotropic agents, such as bafilomycin A1.

conclusionsOur study identifies a renin-angiotensin system-independent function for the (P)RR in the regulation of LDL metabolism by controlling the levels of SORT1 and LDL receptor.

Indexed as

EndocytosisProteomicsAdaptor Proteins, Vesicular TransportAnimalsCHO CellsChromatin ImmunoprecipitationCricetulusHEK293 CellsHepatocytesHep G2 CellsHumansLipoproteins, LDLProrenin ReceptorProtein Processing, Post-TranslationalProteolysisReceptors, Cell SurfaceAdaptor Proteins, Vesicular TransportATP6AP2 protein, humanLDLR protein, humanLipoproteins, LDLProrenin ReceptorReceptors, Cell SurfaceReceptors, LDLSortilinVacuolar Proton-Translocating ATPasescholesterol homeostasisendocytosisLDL receptorsrenin–angiotensin systemsortilin

Identifiers

PMID26582775
OpenAlexW2172668126

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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.