Evidence map›Paper›PMID 23792461›Full record

ArticleThe Journal of investigative dermatology2014

Recombinant filaggrin is internalized and processed to correct filaggrin deficiency.

Thomas E Stout, Trevor McFarland, John C Mitchell, Binoy Appukuttan, J Timothy Stout

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in The Journal of investigative dermatology, 2014. 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
7.4field-weighted citation impact, top 3% 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, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. The Discovery and Function of Filaggrin.International journal of molecular sciences · 2022
    Review
  7. Review
  8. Cracking the Skin Barrier: Liquid-Liquid Phase Separation Shines under the Skin.JID innovations : skin science from molecules to population health · 2021
    Review
  9. Review
  10. Article
  11. Article
  12. Filaggrin and atopic march.Biochemia medica · 2019
    Review
  13. Review
  14. Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis.Clinical, cosmetic and investigational dermatology · 2017
    Article
  15. Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis.International journal of molecular sciences · 2016
    Review
  16. Article
  17. Review
  18. Skin barrier defects in atopic dermatitis.Current allergy and asthma reports · 2014
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Thomas E StoutCasey Eye Institute, Oregon Health and Sciences University, Portland, Oregon, USA. Electronic address: stoutt@ohsu.edu.
Trevor McFarlandCasey Eye Institute, Oregon Health and Sciences University, Portland, Oregon, USA.
John C MitchellDepartment of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA.
Binoy AppukuttanCasey Eye Institute, Oregon Health and Sciences University, Portland, Oregon, USA.
J Timothy StoutCasey Eye Institute, Oregon Health and Sciences University, Portland, Oregon, USA.
Oregon Health & Science University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study was designed to engineer a functional filaggrin (FLG) monomer linked to a cell-penetrating peptide (RMR) and to test the ability of this peptide to penetrate epidermal tissue as a therapeutic strategy for genetically determined atopic dermatitis (AD). A single repeat of the murine filaggrin gene (Flg) was covalently linked to a RMR motif and cloned into a bacterial expression system for protein production. Purified FLG+RMR (mFLG+RMR) was applied in vitro to HEK-293T cells and a reconstructed human epidermis (RHE) tissue model. Immunochemistry demonstrated RMR-dependent cellular uptake of FLG+RMR in a dose- and time-dependent manner in HEK cells. Immunohistochemical staining of the RHE model identified penetration of FLG+RMR to the stratum granulosum, the epidermal layer at which FLG deficiency is thought to be pathologically relevant. In vivo application of FLG+RMR to FLG-deficient flaky tail (ft/ft) mice skin demonstrated internalization and processing of recombinant FLG+RMR to restore the normal phenotype. These results suggest that topically applied RMR-linked FLG monomers are able to penetrate epidermal tissue, be internalized into the appropriate cell type, and be processed to a size similar to wild-type functional barrier peptides to restore necessary barrier function, and prove to be therapeutic for patients with AD.

Indexed as

AnimalsDermatitis, AtopicDermisEpidermal CellsEpidermisFilaggrin ProteinsGenetic TherapyHEK293 CellsHumansIntermediate Filament ProteinsMiceMice, Inbred C57BLMice, Mutant StrainsPhenotypeRecombinant ProteinsFilaggrin ProteinsFLG protein, humanIntermediate Filament ProteinsRecombinant Proteins

Identifiers

PMID23792461
OpenAlexW2073457685

What OpenQuestion holds

Textmetadata
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.