{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T06:43:59Z","timestamp":1765089839185,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]},{"name":"European Union\u2014NextGenerationEU","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]},{"name":"INNOREN-CM: Nuevas estrategias diagn\u00f3sticas y terap\u00e9uticas en enfermedad renal cr\u00f3nica","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]},{"name":"Juan de la Cierva incorporaci\u00f3n","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]},{"name":"Sociedad Espa\u00f1ola de Nefrolog\u00ed","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]},{"name":"European Union\u2019s Horizon 2020","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]},{"name":"Ministero della Salute, Ricerca Corrente","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]},{"name":"European Union\u2014NextGenerationEU","award":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"],"award-info":[{"award-number":["PI20\/00140","DTS20\/00083","PI19\/00815","RD21\/0005\/0002","RD21\/0005\/0017","P2022\/BMD-7221","IJC2018-035187-I","812699","CUP B53C22004000006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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\u2013adaptive 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-\u03baB (NF-\u03baB) 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\u2019 effluent-derived primary mesothelial cells and on the MeT-5A cell line. JQ1 inhibited tumor necrosis factor-\u03b1 (TNF-\u03b1)-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.<\/jats:p>","DOI":"10.3390\/antiox12122055","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T03:48:24Z","timestamp":1701229704000},"page":"2055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2767-0229","authenticated-orcid":false,"given":"Vanessa","family":"Marchant","sequence":"first","affiliation":[{"name":"Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"},{"name":"RICORS2040, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7327-194X","authenticated-orcid":false,"given":"Flavia","family":"Trionfetti","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"},{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4295-7284","authenticated-orcid":false,"given":"Lucia","family":"Tejedor-Santamaria","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"},{"name":"RICORS2040, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6874-2359","authenticated-orcid":false,"given":"Sandra","family":"Rayego-Mateos","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"},{"name":"RICORS2040, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8428-8763","authenticated-orcid":false,"given":"Dante","family":"Rotili","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Bontempi","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"},{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Domenici","sequence":"additional","affiliation":[{"name":"Renal Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6395-6227","authenticated-orcid":false,"given":"Paolo","family":"Men\u00e8","sequence":"additional","affiliation":[{"name":"Renal Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-2382","authenticated-orcid":false,"given":"Antonello","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catalina","family":"Mart\u00edn-Cleary","sequence":"additional","affiliation":[{"name":"Laboratory of Nephrology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-9523","authenticated-orcid":false,"given":"Alberto","family":"Ortiz","sequence":"additional","affiliation":[{"name":"RICORS2040, 28029 Madrid, Spain"},{"name":"Laboratory of Nephrology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian M.","family":"Ramos","sequence":"additional","affiliation":[{"name":"RICORS2040, 28029 Madrid, Spain"},{"name":"Laboratory of Nephrology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3483-8381","authenticated-orcid":false,"given":"Raffaele","family":"Strippoli","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"},{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-6535","authenticated-orcid":false,"given":"Marta","family":"Ruiz-Ortega","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"},{"name":"RICORS2040, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/ckj\/sfab170","article-title":"RICORS2040: The Need for Collaborative Research in Chronic Kidney Disease","volume":"15","author":"Ortiz","year":"2022","journal-title":"Clin. Kidney J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1016\/S0140-6736(14)60384-6","article-title":"Epidemiology, Contributors to, and Clinical Trials of Mortality Risk in Chronic Kidney Failure","volume":"383","author":"Ortiz","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Trionfetti, F., Marchant, V., Gonz\u00e1lez-Mateo, G.T., Kawka, E., M\u00e1rquez-Exp\u00f3sito, L., Ortiz, A., L\u00f3pez-Cabrera, M., Ruiz-Ortega, M., and Strippoli, R. (2023). Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065763"},{"key":"ref_4","first-page":"473134","article-title":"Mesenchymal Conversion of Mesothelial Cells Is a Key Event in the Pathophysiology of the Peritoneum during Peritoneal Dialysis","volume":"2014","year":"2014","journal-title":"Adv. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3543678","DOI":"10.1155\/2016\/3543678","article-title":"Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis","volume":"2016","author":"Strippoli","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1177\/0896860820938239","article-title":"Peritoneal Fibrosis and Epigenetic Modulation","volume":"41","author":"Wang","year":"2021","journal-title":"Perit. Dial. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/path.5352","article-title":"Genetic or Pharmacologic Blockade of Enhancer of Zeste Homolog 2 Inhibits the Progression of Peritoneal Fibrosis","volume":"250","author":"Shi","year":"2020","journal-title":"J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Maeda, K., Doi, S., Nakashima, A., Nagai, T., Irifuku, T., Ueno, T., and Masaki, T. (2017). Inhibition of H3K9 Methyltransferase G9a Ameliorates Methylglyoxal-Induced Peritoneal Fibrosis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173706"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"88730","DOI":"10.18632\/oncotarget.20982","article-title":"Histone Deacetylase 6 Inhibition Counteracts the Epithelial-Mesenchymal Transition of Peritoneal Mesothelial Cells and Prevents Peritoneal Fibrosis","volume":"8","author":"Xu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8492","DOI":"10.1038\/s41598-018-26319-2","article-title":"HDAC1 Inhibition by MS-275 in Mesothelial Cells Limits Cellular Invasion and Promotes MMT Reversal","volume":"8","author":"Rossi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/s41419-022-05398-0","article-title":"Restoration of WT1\/MiR-769-5p Axis by HDAC1 Inhibition Promotes MMT Reversal in Mesenchymal-like Mesothelial Cells","volume":"13","author":"Bontempi","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cheung, K.L., Kim, C., and Zhou, M.M. (2021). The Functions of BET Proteins in Gene Transcription of Biology and Diseases. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.728777"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cell.2009.05.047","article-title":"Control of Inducible Gene Expression by Signal-Dependent Transcriptional Elongation","volume":"138","author":"Hargreaves","year":"2009","journal-title":"Cell"},{"key":"ref_14","first-page":"320","article-title":"Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers","volume":"152","author":"Hoke","year":"2013","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gajjela, B.K., and Zhou, M.M. (2023). Bromodomain Inhibitors and Therapeutic Applications. Curr. Opin. Chem. Biol., 75.","DOI":"10.1016\/j.cbpa.2023.102323"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1681\/ASN.2015080910","article-title":"Inhibition of Bromodomain and Extraterminal Domain Family Proteins Ameliorates Experimental Renal Damage","volume":"28","author":"Rodriguez","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1177\/2040620715576662","article-title":"Inhibition of Bromodomain and Extra-Terminal Proteins (BET) as a Potential Therapeutic Approach in Haematological Malignancies: Emerging Preclinical and Clinical Evidence","volume":"6","author":"Chaidos","year":"2015","journal-title":"Ther. Adv. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nishimura, K., Ogawa, K., Kawaguchi, M., Fumoto, S., Mukai, H., and Kawakami, S. (2021). Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010115"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s12020-019-02115-4","article-title":"BET Bromodomain Inhibition Suppresses Adipogenesis in Mice","volume":"67","author":"Duan","year":"2020","journal-title":"Endocrine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/089686080602600103","article-title":"Ex Vivo Analysis of Dialysis Effluent-Derived Mesothelial Cells as an Approach to Unveiling the Mechanism of Peritoneal Membrane Failure","volume":"26","author":"Aguilera","year":"2006","journal-title":"Perit. Dial. Int."},{"key":"ref_21","first-page":"63903","article-title":"A Mice Model of Chlorhexidine Gluconate-Induced Peritoneal Damage","volume":"2022","author":"Chang","year":"2022","journal-title":"J. Vis. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"724141","DOI":"10.3389\/fphar.2021.724141","article-title":"Blockade of Autophagy Prevents the Development and Progression of Peritoneal Fibrosis","volume":"12","author":"Shi","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"899140","DOI":"10.3389\/fimmu.2022.899140","article-title":"Pharmacologic Inhibition of Histone Deacetylase 6 Prevents the Progression of Chlorhexidine Gluconate-Induced Peritoneal Fibrosis by Blockade of M2 Macrophage Polarization","volume":"13","author":"Shi","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3747\/pdi.2013.00089","article-title":"Saha Suppresses Peritoneal Fibrosis in Mice","volume":"35","author":"Io","year":"2015","journal-title":"Perit. Dial. Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Stergar, J., Dolenec, R., Kojc, N., Lakota, K., Per\u0161e, M., Tom\u0161i\u010d, M., and Milanic, M. (2020). Hyperspectral Evaluation of Peritoneal Fibrosis in Mouse Models. Biomed. Opt. Express, 11.","DOI":"10.1364\/BOE.387837"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"804899","DOI":"10.3389\/fmed.2022.804899","article-title":"Therapeutic Targeting of GSK3\u03b2-Regulated Nrf2 and NF\u03baB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis","volume":"9","author":"Zhou","year":"2022","journal-title":"Front. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1038\/s41374-022-00834-3","article-title":"Parthenolide Alleviates Peritoneal Fibrosis by Inhibiting Inflammation via the NF-\u039aB\/ TGF-\u03b2\/Smad Signaling Axis","volume":"102","author":"Zhang","year":"2022","journal-title":"Lab. Investig."},{"key":"ref_28","first-page":"1452696","article-title":"PGC-1 \u03b1, Inflammation, and Oxidative Stress: An Integrative View in Metabolism","volume":"2020","author":"Ortega","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"To, K.K.W., Xing, E., Larue, R.C., and Li, P.K. (2023). BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications. Molecules, 28.","DOI":"10.3390\/molecules28073043"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s40256-018-00315-3","article-title":"How Might Bromodomain and Extra-Terminal (BET) Inhibitors Operate in Cardiovascular Disease?","volume":"19","author":"Schooling","year":"2019","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12943-018-0915-9","article-title":"BRD4 and Cancer: Going beyond Transcriptional Regulation","volume":"17","author":"Donati","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1038\/nature09589","article-title":"Suppression of Inflammation by a Synthetic Histone Mimic","volume":"468","author":"Nicodeme","year":"2010","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3389\/fphar.2019.01315","article-title":"Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases","volume":"10","author":"Tejedor","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1681\/ASN.V7102192","article-title":"Establishment and Functional Characterization of Human Peritoneal Fibroblasts in Culture: Regulation of Interleukin-6 Production by Proinflammatory Cytokines","volume":"7","author":"Ludat","year":"1996","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1177\/089686089901900307","article-title":"High Glucose Solution and Spent Dialysate Stimulate the Synthesis of Transforming Growth Factor-\u03921 of Human Peritoneal Mesothelial Cells: Effect of Cytokine Costimulation","volume":"19","author":"Kang","year":"1999","journal-title":"Perit. Dial. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.kint.2018.12.030","article-title":"CX3CL1\u2013CX3CR1 Interaction Mediates Macrophage-Mesothelial Cross Talk and Promotes Peritoneal Fibrosis","volume":"95","author":"Helmke","year":"2019","journal-title":"Kidney Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"821681","DOI":"10.3389\/fimmu.2022.821681","article-title":"Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy","volume":"13","author":"Catar","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.molimm.2017.12.023","article-title":"A Pathogenetic Role for M1 Macrophages in Peritoneal Dialysis-Associated Fibrosis","volume":"94","author":"Li","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.kint.2016.03.040","article-title":"Preventing Peritoneal Membrane Fibrosis in Peritoneal Dialysis Patients","volume":"90","author":"Zhou","year":"2016","journal-title":"Kidney Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"688060","DOI":"10.3389\/fmed.2021.688060","article-title":"Role of Macrophages and Related Cytokines in Kidney Disease","volume":"8","author":"Orejudo","year":"2021","journal-title":"Front. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eaaz9705","DOI":"10.1126\/scitranslmed.aaz9705","article-title":"Lithium Preserves Peritoneal Membrane Integrity by Suppressing Mesothelial Cell AB-Crystallin","volume":"13","author":"Herzog","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e22632","DOI":"10.1096\/fj.202200784R","article-title":"Inflammatory Chemokine (C-C Motif) Ligand 8 Inhibition Ameliorates Peritoneal Fibrosis","volume":"37","author":"Lee","year":"2023","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110942","DOI":"10.1016\/j.intimp.2023.110942","article-title":"BET Proteins Inhibitor JQ1 Impairs GM-CSF-Promoted Peritoneal Macrophage Self-Renewal and IL-4-Induced Alternative Polarization","volume":"124","author":"Chen","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/path.5350","article-title":"Inflammatory Macrophages Switch to CCL17-Expressing Phenotype and Promote Peritoneal Fibrosis","volume":"250","author":"Chen","year":"2020","journal-title":"J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1161\/01.RES.0000244015.10655.3f","article-title":"RhoA Mediates Angiotensin II-Induced Phospho-Ser536 Nuclear Factor \u039aB\/RelA Subunit Exchange on the Interleukin-6 Promoter in VSMCs","volume":"99","author":"Cui","year":"2006","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1128\/MCB.01365-08","article-title":"Brd4 Coactivates Transcriptional Activation of NF-\u039aB via Specific Binding to Acetylated RelA","volume":"29","author":"Huang","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wu, X., Qi, J., Bradner, J.E., Xiao, G., and Chen, L.F. (2013). Bromodomain and Extraterminal (BET) Protein Inhibition Suppresses Human T Cell Leukemia Virus 1 (HTLV-1) Tax Protein-Mediated Tumorigenesis by Inhibiting Nuclear Factor \u039aB (NF-\u039aB) Signaling. J. Biol. Chem., 288.","DOI":"10.1074\/jbc.M113.485029"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3747\/pdi.2016.00138","article-title":"TNF Signaling in Peritoneal Mesothelial Cells: Pivotal Role of CFLIPL","volume":"37","author":"Heide","year":"2017","journal-title":"Perit. Dial. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"106064","DOI":"10.1016\/j.intimp.2019.106064","article-title":"Parthenolide, an NF-\u039aB Inhibitor, Alleviates Peritoneal Fibrosis by Suppressing the TGF-\u03b2\/Smad Pathway","volume":"78","author":"Zhang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa020809","article-title":"Peritoneal Dialysis and Epithelial-to-Mesenchymal Transition of Mesothelial Cells","volume":"348","author":"Selgas","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1161\/CIRCRESAHA.119.315125","article-title":"Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation","volume":"125","author":"Stratton","year":"2019","journal-title":"Circ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.12688\/f1000research.11339.1","article-title":"BRD4 Inhibition for the Treatment of Pathological Organ Fibrosis","volume":"6","author":"McKinsey","year":"2017","journal-title":"F1000Research"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hao, K., Jiang, W., Zhou, M., Li, H., Chen, Y., Jiang, F., and Hu, Q. (2020). Targeting BRD4 Prevents Acute Gouty Arthritis by Regulating Pyroptosis. Int. J. Biol. Sci., 16.","DOI":"10.7150\/ijbs.46153"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhang, P., Li, R., Xiao, H., Liu, W., Zeng, X., Xie, G., Yang, W., Shi, L., Yin, Y., and Tao, K. (2019). BRD4 Inhibitor AZD5153 Suppresses the Proliferation of Colorectal Cancer Cells and Sensitizes the Anticancer Effect of PARP Inhibitor. Int. J. Biol. Sci., 15.","DOI":"10.7150\/ijbs.34162"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Liu, H., Wang, L., Weng, X., Chen, H., Du, Y., Diao, C., Chen, Z., and Liu, X. (2019). Inhibition of Brd4 Alleviates Renal Ischemia\/Reperfusion Injury-Induced Apoptosis and Endoplasmic Reticulum Stress by Blocking FoxO4-Mediated Oxidative Stress. Redox Biol., 24.","DOI":"10.1016\/j.redox.2019.101195"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zhou, B., Mu, J., Gong, Y., Lu, C., Zhao, Y., He, T., and Qin, Z. (2017). Brd4 Inhibition Attenuates Unilateral Ureteral Obstruction-Induced Fibrosis by Blocking TGF-\u03b2-Mediated Nox4 Expression. Redox Biol., 11.","DOI":"10.1016\/j.redox.2016.12.031"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Morgado-Pascual, J.L., Suarez-Alvarez, B., Marchant, V., Basantes, P., Tharaux, P.L., Ortiz, A., Lopez-Larrea, C., Ruiz-Ortega, M., and Rayego-Mateos, S. (2023). Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010486"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"111507","DOI":"10.1016\/j.yexcr.2019.111507","article-title":"Bromodomain-Containing Protein 4 Contributes to Renal Fibrosis through the Induction of Epithelial-Mesenchymal Transition","volume":"383","author":"Wang","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1158\/1541-7786.MCR-17-0568","article-title":"BET Proteins Exhibit Transcriptional and Functional Opposition in the Epithelial-to-Mesenchymal Transition","volume":"16","author":"Andrieu","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41420-018-0066-1","article-title":"BRD4 Inhibitor JQ1 Inhibits and Reverses Mechanical Injury-Induced Corneal Scarring","volume":"4","author":"Qu","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41419-020-2431-2","article-title":"Inhibition of BRD4 Prevents Proliferation and Epithelial\u2013Mesenchymal Transition in Renal Cell Carcinoma via NLRP3 Inflammasome-Induced Pyroptosis","volume":"11","author":"Tan","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tamura, R., Doi, S., Nakashima, A., Sasaki, K., Maeda, K., Ueno, T., and Masaki, T. (2018). Inhibition of the H3K4 Methyltransferase SET7\/9 Ameliorates Peritoneal Fibrosis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196844"},{"key":"ref_63","first-page":"2746","article-title":"Histone Acetyltransferase Inhibitor C646 Reverses Epithelial to Mesenchymal Transition of Human Peritoneal Mesothelial Cells via Blocking TGF-\u03921\/Smad3 Signaling Pathway in Vitro","volume":"8","author":"Yang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Aranda-Rivera, A.K., Cruz-Gregorio, A., Aparicio-Trejo, O.E., and Pedraza-Chaverri, J. (2021). Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases. Biomolecules, 11.","DOI":"10.3390\/biom11081144"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","article-title":"NF-\u039aB in Oxidative Stress","volume":"7","author":"Lingappan","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5690","DOI":"10.1038\/s41598-017-05836-6","article-title":"Metformin Ameliorates the Phenotype Transition of Peritoneal Mesothelial Cells and Peritoneal Fibrosis via a Modulation of Oxidative Stress","volume":"7","author":"Shin","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.arr.2013.01.008","article-title":"Mesothelial Cell: A Multifaceted Model of Aging","volume":"12","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_68","first-page":"34","article-title":"Epithelial-to-Mesenchymal Transdifferentiation of Peritoneal Mesothelial Cells Mediated by Oxidative Stress in Peritoneal Fibrosis Rats","volume":"36","author":"Duan","year":"2011","journal-title":"J. Cent. South Univ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1111\/jcmm.17871","article-title":"Astragaloside IV Ameliorates Peritoneal Fibrosis by Promoting PGC-1\u03b1 to Reduce Apoptosis in Vitro and in Vivo","volume":"27","author":"Xie","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1021\/acs.jproteome.2c00713","article-title":"Proteomic Characterization of Peritoneal Extracellular Vesicles in a Mouse Model of Peritoneal Fibrosis","volume":"22","author":"Huang","year":"2023","journal-title":"J. Proteome Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"642793","DOI":"10.1155\/2014\/642793","article-title":"High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells","volume":"2014","author":"Hung","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1038\/s41418-022-00967-4","article-title":"Inhibition of CGAS-STING by JQ1 Alleviates Oxidative Stress-Induced Retina Inflammation and Degeneration","volume":"29","author":"Zou","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"682","DOI":"10.25122\/jml-2022-0287","article-title":"The Effect of JQ1 Systemic Administration on Oxidative Stress and Apoptotic Markers in Renal Ischemic Reperfusion Injury in a Rat Model","volume":"16","author":"Younis","year":"2023","journal-title":"J. Med. Life"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rayego-Mateos, S., Basantes, P., Morgado-Pascual, J.L., Prieto, B.B., Suarez-Alvarez, B., Ortiz, A., Lopez-Larrea, C., and Ruiz-Ortega, M. (2023). BET Protein Inhibitor JQ1 Modulates Mitochondrial Dysfunction and Oxidative Stress Induced by Chronic Kidney Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12051130"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"An, Q.D., Li, Y.Y., Zhang, H.X., Lu, J., Yu, X.D., Lin, Q., and Zhang, Y.G. (2018). Inhibition of Bromodomain-Containing Protein 4 Ameliorates Oxidative Stress\u2013Mediated Apoptosis and Cartilage Matrix Degeneration through Activation of NF-E2\u2013Related Factor 2-Heme Oxygenase-1 Signaling in Rat Chondrocytes. J. Cell Biochem., 119.","DOI":"10.1002\/jcb.27122"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e1195","DOI":"10.1038\/cddis.2014.157","article-title":"The Bromodomain Protein BRD4 Regulates the KEAP1\/NRF2-Dependent Oxidative Stress Response","volume":"5","author":"Hussong","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"F469","DOI":"10.1152\/ajprenal.00527.2017","article-title":"Protective Effect of the BET Protein Inhibitor JQ1 in Cisplatin-Induced Nephrotoxicity","volume":"315","author":"Sun","year":"2018","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Fahey, J.M., Stancill, J.S., Smith, B.C., and Girotti, A.W. (2018). Nitric Oxide Antagonism to Glioblastoma Photodynamic Therapy and Mitigation Thereof by BET Bromodomain Inhibitor JQ1. J. Biol. Chem., 293.","DOI":"10.1074\/jbc.RA117.000443"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1111\/cas.15061","article-title":"Bromodomain-Containing Protein 4 Inhibitor JQ1 Promotes Melanoma Cell Apoptosis by Regulating Mitochondrial Dynamics","volume":"112","author":"Li","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1172\/jci.insight.137127","article-title":"Brd4-P300 Inhibition Downregulates Nox4 and Accelerates Lung Fibrosis Resolution in Aged Mice","volume":"5","author":"Sanders","year":"2020","journal-title":"JCI Insight"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Guerrero-Hue, M., Rayego-Mateos, S., V\u00e1zquez-Carballo, C., Palomino-Antol\u00edn, A., Garc\u00eda-Caballero, C., Opazo-Rios, L., Morgado-Pascual, J.L., Herencia, C., Mas, S., and Ortiz, A. (2021). Protective Role of Nrf2 in Renal Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10010039"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.lfs.2016.07.018","article-title":"Diabetes and Exposure to Peritoneal Dialysis Solutions Alter Tight Junction Proteins and Glucose Transporters of Rat Peritoneal Mesothelial Cells","volume":"161","author":"Venegas","year":"2016","journal-title":"Life Sci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhao, J., Shi, J., Shan, Y., Yu, M., Zhu, X., Zhu, Y., Liu, L., and Sheng, M. (2020). Asiaticoside Inhibits TGF-\u03921-Induced Mesothelial-Mesenchymal Transition and Oxidative Stress via the Nrf2\/HO-1 Signaling Pathway in the Human Peritoneal Mesothelial Cell Line HMrSV5. Cell Mol. Biol. Lett., 25.","DOI":"10.1186\/s11658-020-00226-9"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Zaza, G., Granata, S., Masola, V., Rugiu, C., Fantin, F., Gesualdo, L., Schena, F.P., and Lupo, A. (2013). Downregulation of Nuclear-Encoded Genes of Oxidative Metabolism in Dialyzed Chronic Kidney Disease Patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077847"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.4049\/jimmunol.1301984","article-title":"Bromodomain and Extraterminal Proteins Suppress NF-E2\u2013Related Factor 2\u2013Mediated Antioxidant Gene Expression","volume":"192","author":"Michaeloudes","year":"2014","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13148-021-01069-7","article-title":"Advances in Epigenetic Therapeutics with Focus on Solid Tumors","volume":"13","author":"Jin","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Wang, Z.Q., Zhang, Z.C., Wu, Y.Y., Pi, Y.N., Lou, S.H., Liu, T.B., Lou, G., and Yang, C. (2023). Bromodomain and extraterminal (BET) proteins: Biological functions, diseases, and targeted therapy. Signal Transduct. Target. Ther., 8.","DOI":"10.1038\/s41392-023-01647-6"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/12\/2055\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:33:05Z","timestamp":1760131985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/12\/2055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,29]]},"references-count":87,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["antiox12122055"],"URL":"https:\/\/doi.org\/10.3390\/antiox12122055","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2023,11,29]]}}}