Evidence map›Paper›PMID 30878672›Full record

ArticleThe Journal of investigative dermatology2019

Peptidylarginine Deiminase Inhibitor Cl-Amidine Attenuates Cornification and Interferes with the Regulation of Autophagy in Reconstructed Human Epidermis.

Laura Cau, Hidenari Takahara, Paul R Thompson, Guy Serre, Marie-Claire Méchin, Michel Simon

Open access · greenAbstract read
In one paragraph

Article in The Journal of investigative dermatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 32% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Deimination in epidermal barrier and hair formation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  7. Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  8. Current insights into the role of citrullination in thrombosis.Current opinion in chemical biology · 2023
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. The virtues and vices of protein citrullination.Royal Society open science · 2022
    Review
  14. Article
  15. Deimination, Intermediate Filaments and Associated Proteins.International journal of molecular sciences · 2020
    Review
  16. Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases.International journal of molecular sciences · 2020
    Review
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

6 authors at 3 institutions in 3 countries.

Laura CauUnité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Institut National de la Santé Et de la Recherche Médicale, Université de Toulouse Midi-Pyrénées, Toulouse, France.
Hidenari TakaharaDepartment of Applied Biological Resource Sciences, School of Agriculture, University of Ibaraki, Ibaraki, Japan.
Paul R ThompsonDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Guy SerreUnité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Institut National de la Santé Et de la Recherche Médicale, Université de Toulouse Midi-Pyrénées, Toulouse, France.
Marie-Claire MéchinUnité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Institut National de la Santé Et de la Recherche Médicale, Université de Toulouse Midi-Pyrénées, Toulouse, France.
Michel SimonUnité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Institut National de la Santé Et de la Recherche Médicale, Université de Toulouse Midi-Pyrénées, Toulouse, France. Electronic address: michel.simon@inserm.fr.
Université Fédérale de Toulouse Midi-Pyrénées · FRIbaraki University · JPUniversity of Massachusetts Chan Medical School · US

Funding

Chemical probes to decipher PAD biologyR35GM118112 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Paul R Thompson · 2016 to 2026
$9.5M
NIGMS NIH HHS R35 GM118112
6 · The paper itself

Abstract

Deimination, a post-translational modification catalyzed by a family of enzymes called peptidylarginine deiminases (PADs), is the conversion of arginine into citrulline residues in a protein. Deimination has been associated with numerous physiological and pathological processes. Our aim was to study its implication in the homeostasis of human epidermis, where three PADs are expressed, namely PAD1, 2, and 3. Three-dimensional reconstructed human epidermis (RHEs) were treated for 2 days with increased concentrations (0-800 μM) of Cl-amidine, a specific PAD inhibitor. Cl-amidine treatments inhibited deimination in a dose-dependent manner and were not cytotoxic for keratinocytes. At 800 μM , Cl-amidine was shown to reduce deimination by half, alter keratinocyte differentiation, decrease the number of corneocyte layers, significantly increase the number of transitional cells, induce clustering of mitochondria and of heterogeneous vesicles in the cytoplasm of granular keratinocytes, and upregulate the expression of autophagy proteins, including LC3-II, sestrin-2, and p62/SQSTM1. LC3 and PADs were further shown to partially co-localize in the upper epidermis. These results demonstrated that Cl-amidine treatments slow down cornification and alter autophagy in the granular layer. They suggest that PAD1 and/or PAD3 play a role in the constitutive epidermal autophagy process that appears as an important step in cornification.

Indexed as

ArginineAutophagyCell DifferentiationCells, CulturedCitrullineEpidermisHumansKeratinocytesMicroscopy, Electron, TransmissionOrnithinePrimary Cell CultureProtein-Arginine Deiminase Type 1Protein-Arginine Deiminase Type 3Protein Processing, Post-TranslationalRecombinant ProteinsArginineCitrullineN-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amideOrnithinePADI3 protein, humanProtein-Arginine Deiminase Type 1Protein-Arginine Deiminase Type 3Recombinant Proteins

Identifiers

PMID30878672
PMCPMC6708725
OpenAlexW2921627360

What OpenQuestion holds

Textmetadata
LicenceTDM
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.