Evidence map›Paper›PMID 25157280›Full record

ArticleTheranostics2014

Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing.

Shan Gao, San Hein, Frederik Dagnæs-Hansen, Kathrin Weyer, Chuanxu Yang, Rikke Nielsen, Erik I Christensen, Robert A Fenton, Jørgen Kjems

Open access · goldAbstract read
In one paragraph

Article in Theranostics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
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  5. Nanoparticles in the Treatment of Renal Fibrosis.International journal of nanomedicine · 2026
    Review
  6. Review
  7. Review
  8. Article
  9. Nanotherapeutics in Kidney Disease: Innovations, Challenges, and Future Directions.Journal of the American Society of Nephrology : JASN · 2025
    Review
  10. Review
  11. Gene therapy and kidney diseases.Molecular therapy. Methods & clinical development · 2024
    Review
  12. Efficient and selective kidney targeting by chemically modified carbohydrate conjugates.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  13. Article
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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

9 authors at 1 institution in 1 country.

Shan Gao1. The Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
San Hein1. The Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Frederik Dagnæs-Hansen2. Department of Biomedicine, Aarhus University, Aarhus C, Denmark;
Kathrin Weyer2. Department of Biomedicine, Aarhus University, Aarhus C, Denmark; ; 3. MEMBRANES, Aarhus University, Aarhus C, Denmark;
Chuanxu Yang1. The Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Rikke Nielsen2. Department of Biomedicine, Aarhus University, Aarhus C, Denmark; ; 3. MEMBRANES, Aarhus University, Aarhus C, Denmark;
Erik I Christensen2. Department of Biomedicine, Aarhus University, Aarhus C, Denmark; ; 3. MEMBRANES, Aarhus University, Aarhus C, Denmark;
Robert A Fenton2. Department of Biomedicine, Aarhus University, Aarhus C, Denmark; ; 3. MEMBRANES, Aarhus University, Aarhus C, Denmark; ; 4. Center for Interactions of Proteins in Epithelial Transport, Aarhus University, Aarhus C, Denmark.
Jørgen Kjems1. The Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Aarhus University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered intravenously. Here we confirm by 2D and 3D bioimaging that chitosan formulated siRNA is retained in the kidney for more than 48 hours where it accumulates in proximal tubule epithelial cells (PTECs), a process that was strongly dependent on the molecular weight of chitosan. Chitosan/siRNA nanoparticles, administered to chimeric mice with conditional knockout of the megalin gene, distributed almost exclusively in cells that expressed megalin, implying that the chitosan/siRNA particle uptake was mediated by a megalin-dependent endocytotic pathway. Knockdown of the water channel aquaporin 1 (AQP1) by up to 50% in PTECs was achieved utilizing the systemic i.v. delivery of chitosan/AQP1 siRNA in mice. In conclusion, specific targeting PTECs with the chitosan nanoparticle system may prove to be a useful strategy for knockdown of specific genes in PTECs, and provides a potential therapeutic strategy for treating various kidney diseases.

Indexed as

AnimalsAquaporin 1ChitosanDogsEndocytosisEpithelial CellsGene Knockdown TechniquesKidney Tubules, ProximalLow Density Lipoprotein Receptor-Related Protein-2Madin Darby Canine Kidney CellsMice, KnockoutMolecular WeightNanoparticlesOrgan SpecificityRNA InterferenceRNA, Small InterferingAqp1 protein, mouseAquaporin 1ChitosanLow Density Lipoprotein Receptor-Related Protein-2RNA, Small Interferingaquaporin 1chitosanmegalinoptical imaging.renal targetingsiRNA

Identifiers

PMID25157280
PMCPMC4142293
OpenAlexW2102845556

What OpenQuestion 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 OpenQuestion graph.