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DPC20170139474"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["PJA 20161204650"],"award-info":[{"award-number":["PJA 20161204650"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ARCPJA2021060004010"],"award-info":[{"award-number":["ARCPJA2021060004010"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["R19125AA"],"award-info":[{"award-number":["R19125AA"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCDD"],"abstract":"<jats:p>The Wilms tumor suppressor gene (Wt1) encodes a C2H2-type zinc-finger transcription factor that participates in transcriptional regulation, RNA metabolism, and protein\u2013protein interactions. WT1 is involved in the development of several organs, including the kidneys and gonads, heart, spleen, adrenal glands, liver, diaphragm, and neuronal system. We previously provided evidence of transient WT1 expression in about 25% of cardiomyocytes of mouse embryos. Conditional deletion of Wt1 in the cardiac troponin T lineage caused abnormal cardiac development. A low expression of WT1 has also been reported in adult cardiomyocytes. Therefore, we aimed to explore its function in cardiac homeostasis and in the response to pharmacologically induced damage. Silencing of Wt1 in cultured neonatal murine cardiomyocytes provoked alterations in mitochondrial membrane potential and changes in the expression of genes related to calcium homeostasis. Ablation of WT1 in adult cardiomyocytes by crossing \u03b1MHCMerCreMer mice with homozygous WT1-floxed mice induced hypertrophy, interstitial fibrosis, altered metabolism, and mitochondrial dysfunction. In addition, conditional deletion of WT1 in adult cardiomyocytes increased doxorubicin-induced damage. These findings suggest a novel role of WT1 in myocardial physiology and protection against damage.<\/jats:p>","DOI":"10.3390\/jcdd10050211","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T09:26:13Z","timestamp":1683883573000},"page":"211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cardiomyocyte-Specific Wt1 Is Involved in Cardiac Metabolism and Response to Damage"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-4212","authenticated-orcid":false,"given":"Sandra","family":"D\u00edaz del Moral","sequence":"first","affiliation":[{"name":"Department of Animal Biology, Faculty of Science, University of M\u00e1laga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-6978","authenticated-orcid":false,"given":"Maha","family":"Benaouicha","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Genetics and Physiology, Faculty of Science, University of M\u00e1laga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Villa del Campo","sequence":"additional","affiliation":[{"name":"Cardiovascular Development Program, Centro Nacional de Investigaciones Cardiovasculares, CNIC, 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Torres","sequence":"additional","affiliation":[{"name":"Cardiovascular Development Program, Centro Nacional de Investigaciones Cardiovasculares, CNIC, 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2746-0707","authenticated-orcid":false,"given":"Nicole","family":"Wagner","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, INSERM, iBV, 06108 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-7760","authenticated-orcid":false,"given":"Kay-Dietrich","family":"Wagner","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, INSERM, iBV, 06108 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6392-6802","authenticated-orcid":false,"given":"Ram\u00f3n","family":"Mu\u00f1oz-Ch\u00e1puli","sequence":"additional","affiliation":[{"name":"Department of Animal Biology, Faculty of Science, University of M\u00e1laga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9686-473X","authenticated-orcid":false,"given":"Rita","family":"Carmona","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Legal Medicine and History of Science, Faculty of Medicine, University of M\u00e1laga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1242\/dev.153163","article-title":"Wilms\u2019 tumour 1 (WT1) in development, homeostasis and disease","volume":"144","author":"Hastie","year":"2017","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1101\/gad.346405","article-title":"Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms\u2019 tumor transcription factor Wt1","volume":"19","author":"Wagner","year":"2005","journal-title":"Genes Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/ng.494","article-title":"Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin","volume":"42","author":"Lettice","year":"2010","journal-title":"Nat. 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