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Marchant, VanessaAuthorRayego-Mateos, SandraAuthorOrtiz, AlbertoAuthorRuiz-Ortega, MartaCorresponding Author
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BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress

Publicated to:Antioxidants. 12 (12): 2055- - 2023-12-01 12(12), DOI: 10.3390/antiox12122055

Authors: Marchant, Vanessa; Trionfetti, Flavia; Tejedor-Santamaria, Lucia; Rayego-Mateos, Sandra; Rotili, Dante; Bontempi, Giulio; Domenici, Alessandro; Mene, Paolo; Mai, Antonello; Martin-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrian M; Strippoli, Raffaele; Ruiz-Ortega, Marta

Affiliations

Lazzaro Spallanzani IRCCS, Natl Inst Infect Dis, Gene Express Lab, I-00149 Rome, Italy - Author
Ricors2040, Madrid 28029, Spain - Author
Sapienza Univ Rome, Dept Drug Chem & Technol, I-00185 Rome, Italy - Author
Sapienza Univ Rome, Dept Mol Med, I-00161 Rome, Italy - Author
Sapienza Univ Rome, Sant Andrea Univ Hosp, Renal Unit, Dept Clin & Mol Med, I-00189 Rome, Italy - Author
Univ Autonoma Madrid, Fdn Jimenez Diaz, Sch Med, Cellular & Mol Biol Renal & Vasc Pathol Lab,IIS, Madrid 28040, Spain - Author
Univ Autonoma Madrid, Fdn Jimenez Diaz, Sch Med, Lab Nephrol,IIS, Madrid 28040, Spain - Author
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Abstract

Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead to damage of the peritoneal membrane (PM) through mechanisms involving the activation of the inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading to filtration failure. Peritoneal damage depends on a complex interaction among external stimuli, intrinsic properties of the PM, and subsequent activities of the local innate-adaptive immune system. Epigenetic drugs targeting bromodomain and extra-terminal domain (BET) proteins have shown beneficial effects on different experimental preclinical diseases, mainly by inhibiting proliferative and inflammatory responses. However the effect of BET inhibition on peritoneal damage has not been studied. To this aim, we have evaluated the effects of treatment with the BET inhibitor JQ1 in a mouse model of peritoneal damage induced by chlorhexidine gluconate (CHX). We found that JQ1 ameliorated the CHX-induced PM thickness and inflammatory cell infiltration. Moreover, JQ1 decreased gene overexpression of proinflammatory and profibrotic markers, together with an inhibition of the nuclear factor-kappa B (NF-kappa B) pathway. Additionally, JQ1 blocked the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and restored changes in the mRNA expression levels of NADPH oxidases (NOX1 and NOX4) and NRF2/target antioxidant response genes. To corroborate the in vivo findings, we evaluated the effects of the BET inhibitor JQ1 on PD patients' effluent-derived primary mesothelial cells and on the MeT-5A cell line. JQ1 inhibited tumor necrosis factor-alpha (TNF-alpha)-induced proinflammatory gene upregulation and restored MMT phenotype changes, together with the downmodulation of oxidative stress. Taken together, these results suggest that BET inhibitors may be a potential therapeutic option to ameliorate peritoneal damage.

Keywords
Bet proteinsBromodomainDialysisFibrosisInflammationJq1Mesenchymal transitionMesothelial cellsNf-kappa-bNrf2OxidationPeritoneal damageSuppresses

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Antioxidants 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, 2023, it was in position 8/72, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Medicinal. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-04-28:

  • Europe PMC: 1
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 2025-04-28:

  • 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: 16 (PlumX).

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

    It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

    • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
    Leadership analysis of institutional authors

    This work has been carried out with international collaboration, specifically with researchers from: Italy.

    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 (MARCHANT HERNANDEZ, VANESSA ALEJANDRA) and Last Author (RUIZ ORTEGA, MARTA).

    the author responsible for correspondence tasks has been RUIZ ORTEGA, MARTA.