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Altamirano Gómez, José TrinidadAuthorAffo, SAuthorDominguez, MAuthorSancho-Bru, PAuthorRodrigo-Torres, DCorresponding AuthorMorales-Ibanez, OAuthorMoreno, MAuthorMillan, CAuthorAltamirano, JAuthorGarcia-Pagan, JcAuthorArroyo, VAuthorGines, PAuthorCaballeria, JAuthorBataller, RCorresponding Author
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Article

Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis

Publicated to:Gut. 62 (3): 452-460 - 2013-03-01 62(3), DOI: 10.1136/gutjnl-2011-301146

Authors: Affo, Silvia; Dominguez, Marlene; Jose Lozano, Juan; Sancho-Bru, Pau; Rodrigo-Torres, Daniel; Morales-Ibanez, Oriol; Moreno, Montserrat; Millan, Cristina; Loaeza-del-Castillo, Aurora; Altamirano, Jose; Carlos Garcia-Pagan, Juan; Arroyo, Vicente; Gines, Pere; Caballeria, Juan; Schwabe, Robert F; Bataller, Ramon

Affiliations

CIBER Enfermedades Hepat & Digest CIBERehd, Ctr Esther Koplowitz, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Liver Unit,Hosp Clin, Barcelona, Spain - Author
Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA - Author
Hospital Clinic Barcelona - Author

Abstract

Alcoholic hepatitis (AH) is a severe clinical condition that needs novel therapies. The identification of targets for therapy is hampered by the lack of animal models of advanced AH. The authors performed a translational study through a transcriptome analysis in patients with AH to identify new molecular targets.Hepatic gene expression profiling was assessed by DNA microarray in patients with AH (n=15) and normal livers (n=7). Functional analysis was assessed by gene set enrichment analysis. Quantitative PCR was performed in patients with AH (n=40), hepatitis C (n=18), non-alcoholic steatohepatitis (n=20) and in mouse models of acute and chronic liver injury. Protein expression was assessed by immunohistochemistry and western blotting.Gene expression analysis showed 207 genes >5-fold differentially expressed in patients with AH and revealed seven pathways differentially regulated including 'cytokine-cytokine receptor interaction'. Several tumour necrosis factor (TNF) superfamily receptors, but not ligands, were overexpressed in AH. Importantly, Fn14 was the only TNF superfamily receptor exclusively upregulated in AH compared with other liver diseases and correlated with both 90-day mortality and severity of portal hypertension. Fn14 protein expression was detected in areas of fibrogenesis and in a population of hepatocytes. Fn14 expression was increased in experimental models of liver injury and was detected in progenitor cells.Translational research revealed that TNF superfamily receptors are overexpressed in AH. Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively upregulated in patients with AH. TNF superfamily receptors could represent a potential target for therapy.

Keywords
cytokinesfactor-alphagene-expressionliver-diseasemetaanalysisscoring systemsteatohepatitistweakvalidationAnimalsBlotting, westernBrainCluster analysisCytokinesFactor-alphaFemaleGene expression profilingGene expression regulationGene-expressionHepatitis, alcoholicHumansImmunohistochemistryMaleMetaanalysisMetabolismMiceMice, inbred c57blMicroarray analysisMiddle agedMolecular targeted therapyOwnershipPrognosisProspective studiesReal-time polymerase chain reactionReceptors, tumor necrosis factorScoring systemSignal transductionTherapyTnfrsf12a protein, humanTnfrsf12a protein, mouseTumor-necrosis-factorTweak receptorUp-regulationValidation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Gut 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, 2013, it was in position 2/75, thus managing to position itself as a Q1 (Primer Cuartil), in the category Gastroenterology & Hepatology.

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: 4.4. 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 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 5.47 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 36.52 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-12, the following number of citations:

  • WoS: 169
  • Scopus: 181
  • Europe PMC: 130
  • Google Scholar: 194
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 2025-05-12:

  • 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: 93.
  • 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: 93 (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: 6.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).
Leadership analysis of institutional authors

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

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Affò, Silvia) and Last Author (Bataller Alberola, Ramon).

the authors responsible for correspondence tasks have been Rodrigo Torres, Daniel and Bataller Alberola, Ramon.