{rfName}
He

Indexed in

Altmetrics

Analysis of institutional authors

Chapus, Fleur Lucie StellaAuthor

Share

November 15, 2024
Publications
>
Article
No

Hepatic inflammation elicits production of proinflammatory netrin-1 through exclusive activation of translation

Publicated to: HEPATOLOGY. 76 (5): 1345-1359 - 2022-04-01 76(5), DOI: 10.1002/hep.32446

Authors:

Barnault, Romain; Verzeroli, Claire; Fournier, Carole; Michelet, Maud; Redavid, Anna Rita; Chicherova, Ievgeniia; Plissonnier, Marie-Laure; Adrait, Annie; Khomich, Olga; Chapus, Fleur; Richaud, Mathieu; Hervieu, Maeva; Reiterer, Veronika; Centonze, Federica Grazia; Lucifora, Julie; Bartosch, Birke; Rivoire, Michel; Farhan, Hesso; Coute, Yohann; Mirakaj, Valbona; Decaens, Thomas; Mehlen, Patrick; Gibert, Benjamin; Zoulim, Fabien; Parent, Romain
[+]

Affiliations

Canc Res Ctr Lyon, Canc & Dev Lab LabEx DEVweCAN, Inserm U1052, Apoptosis, Lyon, France - Author
Canc Res Ctr Lyon, Inserm U1052, Lyon, France - Author
Canc Res Ctr Lyon, Pathogenesis Chron Hepatitis B&C Lab LabEx DEVweC, Inserm U1052, Lyon, France - Author
CNRS, UMR5286, Lyon, France - Author
Ctr Leon Berard, Lyon, France - Author
Eberhard Karls Univ Tubingen, Univ Hosp Tuebingen, Dept Anesthesiol & Intens Care Med, Tubingen, Germany - Author
Hosp Civils Lyon, Serv Hepatogastroenterol, Lyon, France - Author
Leon Berard Canc Ctr, Lyon, France - Author
Med Univ Innsbruck, Inst Pathophysiol, Innsbruck, Austria - Author
Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, Single Cell Dynam Grp, Durham, NC USA - Author
Univ Grenoble Alpes, CNRS CEA FR2048, UMR BioSante U1292, CEA,Inserm, Grenoble, France - Author
Univ Grenoble Alpes, Inst Adv Biosci, Inserm U1209, La Tronche, France - Author
Univ Lyon 1, Inst Sci Pharmaceut & Biol, Lyon, France - Author
Univ Lyon 1, Lyon, France - Author
Univ Lyon, Lyon, France - Author
See more

Abstract

Background and Aims Netrin-1 displays protumoral properties, though the pathological contexts and processes involved in its induction remain understudied. The liver is a major model of inflammation-associated cancer development, leading to HCC. Approach and Results A panel of cell biology and biochemistry approaches (reverse transcription quantitative polymerase chain reaction, reporter assays, run-on, polysome fractionation, cross linking immunoprecipitation, filter binding assay, subcellular fractionation, western blotting, immunoprecipitation, stable isotope labeling by amino acids in cell culture) on in vitro-grown primary hepatocytes, human liver cell lines, mouse samples and clinical samples was used. We identify netrin-1 as a hepatic inflammation-inducible factor and decipher its mode of activation through an exhaustive eliminative approach. We show that netrin-1 up-regulation relies on a hitherto unknown mode of induction, namely its exclusive translational activation. This process includes the transfer of NTN1 (netrin-1) mRNA to the endoplasmic reticulum and the direct interaction between the Staufen-1 protein and this transcript as well as netrin-1 mobilization from its cell-bound form. Finally, we explore the impact of a phase 2 clinical trial-tested humanized anti-netrin-1 antibody (NP137) in two distinct, toll-like receptor (TLR) 2/TLR3/TLR6-dependent, hepatic inflammatory mouse settings. We observe a clear anti-inflammatory activity indicating the proinflammatory impact of netrin-1 on several chemokines and Ly6C+ macrophages. Conclusions These results identify netrin-1 as an inflammation-inducible factor in the liver through an atypical mechanism as well as its contribution to hepatic inflammation.
[+]

Keywords

Amino acidsAnimalsAnti-inflammatory agentsBinding proteinCarcinoma, hepatocellularDouble-stranded-rnaExpressionHumansInflammationLiver neoplasmsLocalizesMacrophage infiltrationMessenger-rnaMiceNerve growth factorsNetrin receptorsPharmacological inhibitionReceptorsRna, messengerStaufenSurvivaToll-like receptor 2Toll-like receptor 3Toll-like receptor 6Tumor suppressor proteins

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal HEPATOLOGY due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 6/93, thus managing to position itself as a Q1 (Primer Cuartil), in the category Gastroenterology & Hepatology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.01. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-04, the following number of citations:

  • WoS: 10
  • Europe PMC: 8
[+]

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-04:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 12.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 9.
  • The number of mentions on the social network X (formerly Twitter): 5 (Altmetric).
[+]

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Austria; France; Germany; United States of America.

[+]

Awards linked to the item

Romain Barnault and Ievgeniia Chicherova are recipients of a DevWeCan Labex (Laboratories of Excellence Network, ANR-LABX-061) and Agence Nationale de la Recherche sur le Sida et les Hepatites Virales (ECTZ63958) predoctoral fellowships, respectively. Funding was obtained through the same Labex consortium (ANR-LABX-061) and the French National Cancer Institute (Inca PRT-K 19-033). Proteomic experiments were partially supported by the French National Research Agency under projects ProFI (Proteomics French Infrastructure, ANR-10-INBS-08) and GRAL, a program from the Chemistry Biology Health Graduate School of University of Grenoble-Alps (ANR-17-EURE-0003)
[+]