{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:32:13Z","timestamp":1786692733679,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Aging is a major risk factor for cardiovascular diseases (CVD), partly due to the accumulation of senescent cells. Senescence is characterized by irreversible cell cycle arrest and the acquisition of a senescence associated secretory phenotype (SASP), which promotes inflammation and tissue remodeling, thereby contributing to cardiac dysfunction. Cardiac fibroblasts (CFs), key regulators of cardiac repair, differentiate into myofibroblasts (CMFs) in response to pathological stimuli such as mechanical stiffness and TGF-\u03b21. CMFs secrete abundant extracellular matrix (ECM) proteins, and while their senescence may transiently restrict fibrosis in acute cardiac injury, persistent senescence promotes chronic remodeling through SASP activity. Given that TGF-\u03b21 is a central mediator of CF-to-CMF differentiation and can induce senescence in various cell lines, we investigated whether it simultaneously triggers both processes in neonatal rat CFs, and whether the senotherapeutics Navitoclax and Dasatinib + Quercetin modulate the viability of senescent CMFs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CF from neonatal rats were incubated in DMEM-F12 (10% FBS), and treated with TGF-\u03b21 (10 46 ng\/mL, 7 days). Proteins were analyzed by Western blot and immunocytochemistry. Cytokines were analyzed by Milliplex. After 7 days cells were treated with senolytics drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CFs treated with TGF-\u03b21 exhibited senescence markers (p15-p16, p21), increased SA-\u03b2-gal activity, and reduced Ki-67 and p-Rb expression. CMFs displayed enhanced secretion of IL-1\u03b2, IL-6, IL-5, and IL-10, together with elevated collagen and VCAM-1 levels, indicating a pro-fibrotic and low-grade inflammatory phenotype. Treatment with Navitoclax or Dasatinib + Quercetin decreased cell viability and reduced the proportion of SA-\u03b2-gal -positive cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TGF-\u03b21 simultaneously promotes CF differentiation into CMFs and induces senescence, resulting in a sustained pro-fibrotic and inflammatory phenotype. Senotherapeutics treatment attenuates senescent CMFs, supporting its potential as a therapeutic strategy to mitigate cardiac fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1877172","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:11:55Z","timestamp":1786691515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Simultaneous induction of differentiation and senescence in cardiac fibroblasts by TGF-\u03b21: effects of senotherapeutics drugs"],"prefix":"10.3389","volume":"17","author":[{"given":"Claudio","family":"Espinoza-Perez","sequence":"first","affiliation":[{"name":"Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel","family":"Osorio","sequence":"additional","affiliation":[{"name":"Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"V\u00e9lez","sequence":"additional","affiliation":[{"name":"Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Ortega Bustos","sequence":"additional","affiliation":[{"name":"Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Machuca","sequence":"additional","affiliation":[{"name":"Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Rivas","sequence":"additional","affiliation":[{"name":"Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F.","family":"S\u00e1nchez-Ferrer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid","place":["Madrid, Spain"]},{"name":"Instituto de Investigaciones Sanitarias IdiPAZ","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Peir\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid","place":["Madrid, Spain"]},{"name":"Instituto de Investigaciones Sanitarias IdiPAZ","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Vivar","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Pharmacology Program, Biomedical Sciences Institute, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"D\u00edaz-Araya","sequence":"additional","affiliation":[{"name":"Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile","place":["Santiago, Chile"]},{"name":"Advanced Center for Chronic Diseases, Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, University of Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1093\/cvr\/cvab161","article-title":"Senescence mechanisms and targets in the heart","volume":"118","author":"Chen","year":"2022","journal-title":"Cardiovasc. 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