{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:59:43Z","timestamp":1785117583952,"version":"3.55.0"},"reference-count":81,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The adult mammalian heart exhibits limited regenerative capacity. Although the epicardium contributes to cardiac injury responses and remodeling, expandable adult human in vitro models for investigating epicardial activation and epithelial-to-mesenchymal (EMT)-associated cellular responses remain limited. Here, we isolated human epicardium-derived cells from the adult heart auricle, expressing WT1+\/MSLN+\/CRIP1+ and generated an expandable immortalized epicardium-derived cell (iEPDC) population, allowing the investigation of intercellular dynamics upon EMT activation. TGF\u03b2 signaling was modulated using SB431542 or TGF\u03b23. Morphological, immunocytochemical, transcriptomic and functional analyses were performed to investigate treatment-dependent responses. SB431542-treated iEPDCs displayed epithelial-like characteristics and elevated WT1, MSLN and CRIP1 expression, with CRIP1 detected at both transcript and protein levels. TGF\u03b23-treated cells expressed the mesenchymal markers VIM and CD105 and exhibited spindle-shaped morphology, increased migratory behavior and upregulation of mesenchymal- and remodeling-associated markers. Transcriptomic analyses revealed distinct treatment-dependent profiles, enrichment of \u2018focal adhesion\u2019, \u2018ECM-receptor interaction\u2019 and cytoskeleton-associated pathways in TGF\u03b23-treated iEPDCs and intermediate transcriptional characteristics in untreated cells. Together, these findings establish adult iEPDCs as an expandable in vitro model for investigating TGF\u03b2-dependent epicardial activation and EMT-associated processes in the adult human heart. Furthermore, the integration of phenotypic, transcriptomic and functional findings revealed the treatment-responsive plasticity of adult human iEPDCs, supporting future studies of injury-associated epicardial activation.<\/jats:p>","DOI":"10.3390\/cells15141313","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:25:46Z","timestamp":1784726746000},"page":"1313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TGF\u03b2-Dependent Epithelial\u2013Mesenchymal Plasticity in Immortalized Human Atrial Epicardial Cells: An mRNA Profiling Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Katja","family":"Nowak","sequence":"first","affiliation":[{"name":"Ruhr University Bochum, Heart and Diabetes Center NRW, Institute of Laboratory and Transfusion Medicine, 32545 Bad Oeynhausen, Germany"},{"name":"University Bielefeld, Faculty of Biology, Department of Cell Biology, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Schramm","sequence":"additional","affiliation":[{"name":"Ruhr University Bochum, Heart and Diabetes Center NRW, Department of Thoracic and Cardiovascular Surgery, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kaltschmidt","sequence":"additional","affiliation":[{"name":"University Bielefeld, Faculty of Biology, Molecular Neurobiology, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kaltschmidt","sequence":"additional","affiliation":[{"name":"University Bielefeld, Faculty of Biology, Department of Cell Biology, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Knabbe","sequence":"additional","affiliation":[{"name":"Ruhr University Bochum, Heart and Diabetes Center NRW, Institute of Laboratory and Transfusion Medicine, 32545 Bad Oeynhausen, Germany"},{"name":"University Bielefeld, Medical Faculty OWL, Heart and Diabetes Center NRW, Institute of Laboratory and Transfusion Medicine, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-0220","authenticated-orcid":false,"given":"Anna L.","family":"H\u00f6ving","sequence":"additional","affiliation":[{"name":"Ruhr University Bochum, Heart and Diabetes Center NRW, Institute of Laboratory and Transfusion Medicine, 32545 Bad Oeynhausen, Germany"},{"name":"University Bielefeld, Faculty of Biology, Department of Cell Biology, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.cell.2015.05.026","article-title":"Dynamics of Cell Generation and Turnover in the Human Heart","volume":"161","author":"Bergmann","year":"2015","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.cell.2006.08.052","article-title":"A Dynamic Epicardial Injury Response Supports Progenitor Cell Activity during Zebrafish Heart Regeneration","volume":"127","author":"Lepilina","year":"2006","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1172\/JCI45529","article-title":"Adult Mouse Epicardium Modulates Myocardial Injury by Secreting Paracrine Factors","volume":"121","author":"Zhou","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41569-018-0046-4","article-title":"The Epicardium as a Hub for Heart Regeneration","volume":"15","author":"Cao","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"203717","DOI":"10.1016\/j.cdev.2021.203717","article-title":"Getting Started for Migration: A Focus on EMT Cellular Dynamics and Mechanics in Developmental Models","volume":"168","author":"Montemurro","year":"2021","journal-title":"Cells Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41580-020-0237-9","article-title":"Guidelines and Definitions for Research on Epithelial\u2013Mesenchymal Transition","volume":"21","author":"Yang","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1161\/CIRCRESAHA.111.259960","article-title":"Endocardial and Epicardial Epithelial to Mesenchymal Transitions in Heart Development and Disease","volume":"110","author":"Pu","year":"2012","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature07060","article-title":"Epicardial Progenitors Contribute to the Cardiomyocyte Lineage in the Developing Heart","volume":"454","author":"Zhou","year":"2008","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ydbio.2012.04.020","article-title":"Epicardially Derived Fibroblasts Preferentially Contribute to the Parietal Leaflets of the Atrioventricular Valves in the Murine Heart","volume":"366","author":"Wessels","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_10","first-page":"1056","article-title":"Epicardium-Derived Cells (EPDCs) in Development, Cardiac Disease and Repair of Ischemia","volume":"14","author":"Winter","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Van Wijk, B., Gunst, Q.D., Moorman, A.F.M., and Van Den Hoff, M.J.B. (2012). Cardiac Regeneration from Activated Epicardium. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044692"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E8","DOI":"10.1038\/nature07916","article-title":"Tbx18 and the Fate of Epicardial Progenitors","volume":"458","author":"Christoffels","year":"2009","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.yjmcc.2015.02.007","article-title":"Cardiac Endothelial Cells Express Wilms\u2019 Tumor-1","volume":"81","author":"Duim","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1161\/CIRCRESAHA.112.273946","article-title":"Wt1 and Epicardial Fate Mapping","volume":"111","author":"Rudat","year":"2012","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.phrs.2017.07.020","article-title":"The Epicardium as a Source of Multipotent Adult Cardiac Progenitor Cells: Their Origin, Role and Fate","volume":"127","author":"Smits","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Streef, T.J., and Smits, A.M. (2021). Epicardial Contribution to the Developing and Injured Heart: Exploring the Cellular Composition of the Epicardium. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.750243"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ge, Y., Smits, A.M., Liu, J., Zhang, J., van Brakel, T.J., Goumans, M.J.T.H., Jongbloed, M.R.M., and de Vries, A.A.F. (2021). Generation, Characterization, and Application of Inducible Proliferative Adult Human Epicardium-Derived Cells. Cells, 10.","DOI":"10.3390\/cells10082064"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dronkers, E., Moerkamp, A.T., van Herwaarden, T., Goumans, M.-J., and Smits, A.M. (2018). The Isolation and Culture of Primary Epicardial Cells Derived from Human Adult and Fetal Heart Specimens. J. Vis. Exp., 57370.","DOI":"10.3791\/57370"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/0014-4827(65)90211-9","article-title":"The Limited in Vitro Lifetime of Human Diploid Cell Strains","volume":"37","author":"Hayflick","year":"1965","journal-title":"Exp. Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sch\u00e4uble, S., Klement, K., Marthandan, S., M\u00fcnch, S., Heiland, I., Schuster, S., Hemmerich, P., and Diekmann, S. (2012). Quantitative Model of Cell Cycle Arrest and Cellular Senescence in Primary Human Fibroblasts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042150"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1186\/s40064-016-3091-7","article-title":"Detection of Mesenchymal Stem Cells Senescence by Prelamin A Accumulation at the Nuclear Level","volume":"5","author":"Bellotti","year":"2016","journal-title":"SpringerPlus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0735-1097(97)00116-2","article-title":"Induction of Cytokine Expression in Leukocytes in Acute Myocardial Infarction","volume":"30","author":"Marx","year":"1997","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1111\/jcmm.14313","article-title":"The Role and Mechanism of Transforming Growth Factor Beta 3 in Human Myocardial Infarction-induced Myocardial Fibrosis","volume":"23","author":"Xue","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13287-016-0434-9","article-title":"Human Fetal and Adult Epicardial-Derived Cells: A Novel Model to Study Their Activation","volume":"7","author":"Moerkamp","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1111\/j.1582-4934.2011.01266.x","article-title":"Epithelial-to-Mesenchymal Transformation Alters Electrical Conductivity of Human Epicardial Cells","volume":"15","author":"Bax","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dronkers, E., Wauters, M.M.M., Goumans, M.J., and Smits, A.M. (2020). Epicardial TGF\u03b2 and BMP Signaling in Cardiac Regeneration: What Lesson Can We Learn from the Developing Heart?. Biomolecules, 10.","DOI":"10.3390\/biom10030404"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.stemcr.2023.06.002","article-title":"Single-Cell Analysis of Human Fetal Epicardium Reveals Its Cellular Composition and Identifies CRIP1 as a Modulator of EMT","volume":"18","author":"Streef","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.1067081","article-title":"Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors","volume":"295","author":"Lois","year":"2002","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"H\u00f6ving, A.L., Sielemann, K., Greiner, J.F.W., Kaltschmidt, B., Knabbe, C., and Kaltschmidt, C. (2020). Transcriptome Analysis Reveals High Similarities between Adult Human Cardiac Stem Cells and Neural Crest-Derived Stem Cells. Biology, 9.","DOI":"10.3389\/fcell.2021.662754"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Suarez-Arnedo, A., Torres Figueroa, F., Clavijo, C., Arbel\u00e1ez, P., Cruz, J.C., and Mu\u00f1oz-Camargo, C. (2020). An Image J Plugin for the High Throughput Image Analysis of in Vitro Scratch Wound Healing Assays. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232565"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1038\/s44161-022-00183-w","article-title":"A Single-Cell Comparison of Adult and Fetal Human Epicardium Defines the Age-Associated Changes in Epicardial Activity","volume":"1","author":"Davaapil","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/s41586-020-2797-4","article-title":"Cells of the Adult Human Heart","volume":"588","author":"Maatz","year":"2020","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.jpha.2023.07.011","article-title":"Single-Cell and Spatial Heterogeneity Landscapes of Mature Epicardial Cells","volume":"13","author":"Du","year":"2023","journal-title":"J. Pharm. Anal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1161\/CIRCRESAHA.119.315857","article-title":"The Role of the Epicardium During Heart Development and Repair","volume":"126","author":"Quijada","year":"2020","journal-title":"Circ. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1134\/S1990519X2102005X","article-title":"Endoglin Expression and Surface Renewal in Mesenchymal Stem Cells and Endothelial Cells","volume":"15","author":"Pinevich","year":"2021","journal-title":"Cell Tissue Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"H\u00f6ving, A.L., Schmidt, K.E., Merten, M., Hamidi, J., Rott, A.-K., Faust, I., Greiner, J.F.W., Gummert, J., Kaltschmidt, B., and Kaltschmidt, C. (2020). Blood Serum Stimulates P38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells. Cells, 9.","DOI":"10.3390\/cells9061472"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00395-011-0181-0","article-title":"In Vitro Epithelial-to-Mesenchymal Transformation in Human Adult Epicardial Cells Is Regulated by TGF\u03b2-Signaling and WT1","volume":"106","author":"Bax","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_39","first-page":"7443","article-title":"Upregulation of Seladin-1 and Nestin Expression in Bone Marrow Mesenchymal Stem Cell Transplantation via the ERK1\/2 and PI3K\/Akt Signaling Pathways in an Alzheimer\u2019s Disease Model","volume":"15","author":"Yu","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5810465","DOI":"10.1155\/2019\/5810465","article-title":"Roles of the Phosphorylation of Transcriptional Factors in Epithelial-Mesenchymal Transition","volume":"2019","author":"Xu","year":"2019","journal-title":"J. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1038\/s41587-023-01718-7","article-title":"Epicardioid Single-Cell Genomics Uncovers Principles of Human Epicardium Biology in Heart Development and Disease","volume":"41","author":"Meier","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41392-024-01809-0","article-title":"Induced Pluripotent Stem Cells (iPSCs): Molecular Mechanisms of Induction and Applications","volume":"9","author":"Cerneckis","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Koivum\u00e4ki, J.T., Naumenko, N., Tuomainen, T., Takalo, J., Oksanen, M., Puttonen, K.A., Lehtonen, \u0160., Kuusisto, J., Laakso, M., and Koistinaho, J. (2018). Structural Immaturity of Human iPSC-Derived Cardiomyocytes: In Silico Investigation of Effects on Function and Disease Modeling. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00080"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cell.2016.06.028","article-title":"EMT: 2016","volume":"166","author":"Nieto","year":"2016","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1016\/j.celrep.2019.01.079","article-title":"Single-Cell Transcriptome Analysis Maps the Developmental Track of the Human Heart","volume":"26","author":"Cui","year":"2019","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1152\/physiolgenomics.00064.2016","article-title":"Comparative Transcriptomic Analysis Identifies Genes Differentially Expressed in Human Epicardial Progenitors and hiPSC-Derived Cardiac Progenitors","volume":"48","author":"Synnergren","year":"2016","journal-title":"Physiol. Genom."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1161\/hy0202.102835","article-title":"Lipocalin-Type Prostaglandin D Synthase in Essential Hypertension","volume":"39","author":"Hirawa","year":"2002","journal-title":"Hypertension"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Schmidt, K.E., H\u00f6ving, A.L., Kiani Zahrani, S., Trevlopoulou, K., Kaltschmidt, B., Knabbe, C., and Kaltschmidt, C. (2024). Serum-Induced Proliferation of Human Cardiac Stem Cells Is Modulated via TGF\u03b2RI\/II and SMAD2\/3. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020959"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1091\/mbc.e11-02-0103","article-title":"An Autocrine TGF-\u03b2\/ZEB\/miR-200 Signaling Network Regulates Establishment and Maintenance of Epithelial-Mesenchymal Transition","volume":"22","author":"Gregory","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/jcp.21888","article-title":"Matrix Association of Latent TGF-beta Binding Protein-2 (LTBP-2) Is Dependent on Fibrillin-1","volume":"221","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41420-024-01886-8","article-title":"Serpine1 mRNA Confers Mesenchymal Characteristics to the Cell and Promotes CD8+ T Cells Exclusion from Colon Adenocarcinomas","volume":"10","author":"Torres","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3892\/ijo.2020.5153","article-title":"Crosstalk between YAP and TGF\u03b2 Regulates SERPINE1 Expression in Mesenchymal Lung Cancer Cells","volume":"58","author":"Kong","year":"2020","journal-title":"Int. J. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3402","DOI":"10.1172\/JCI97192","article-title":"The Cardiac Lymphatic System Stimulates Resolution of Inflammation Following Myocardial Infarction","volume":"128","author":"Vieira","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/labinvest.3780313","article-title":"Tenascin-C Modulates Adhesion of Cardiomyocytes to Extracellular Matrix during Tissue Remodeling after Myocardial Infarction","volume":"81","author":"Hiroe","year":"2001","journal-title":"Lab. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Sweeney, M., O\u2019Fee, K., Villanueva-Hayes, C., Rahman, E., Lee, M., Vanezis, K., Andrew, I., Lim, W.-W., Widjaja, A., and Barton, P.J.R. (2023). Cardiomyocyte-Restricted Expression of IL11 Causes Cardiac Fibrosis, Inflammation, and Dysfunction. Int. J. Mol. Sci., 24.","DOI":"10.1101\/2023.05.23.541928"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0006-291X(02)02197-6","article-title":"A Role of Heparin-Binding Epidermal Growth Factor-like Growth Factor in Cardiac Remodeling after Myocardial Infarction","volume":"297","author":"Tanaka","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100860","DOI":"10.1016\/j.isci.2020.100860","article-title":"ATF6 Is a Critical Determinant of CHOP Dynamics during the Unfolded Protein Response","volume":"23","author":"Yang","year":"2020","journal-title":"iScience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1038\/s41598-019-39515-5","article-title":"Overlapping and Differential Functions of ATF6\u03b1 versus ATF6\u03b2 in the Mouse Heart","volume":"9","author":"Correll","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.yjmcc.2024.02.001","article-title":"ATF6 Protects against Protein Misfolding during Cardiac Hypertrophy","volume":"189","author":"Hofmann","year":"2024","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1161\/CIRCRESAHA.118.313854","article-title":"ATF6 Regulates Cardiac Hypertrophy by Transcriptional Induction of the mTORC1 Activator","volume":"124","author":"Blackwood","year":"2019","journal-title":"Rheb. Circ. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Schmidt, K.E., H\u00f6ving, A.L., Nowak, K., An Mey, N., Kiani Zahrani, S., Nemeita, B., Riedel, L., Majewski, A., Kaltschmidt, B., and Knabbe, C. (2024). Serum Induces the Subunit-Specific Activation of NF-\u03baB in Proliferating Human Cardiac Stem Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073593"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s13770-023-00536-x","article-title":"Development of Matrix Metalloproteinases-Mediated Extracellular Matrix Remodeling in Regenerative Medicine: A Mini Review","volume":"20","author":"Chen","year":"2023","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1242\/dev.067041","article-title":"Tcf21+ Epicardial Cells Adopt Non-Myocardial Fates during Zebrafish Heart Development and Regeneration","volume":"138","author":"Kikuchi","year":"2011","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature06969","article-title":"A Myocardial Lineage Derives from Tbx18 Epicardial Cells","volume":"454","author":"Cai","year":"2008","journal-title":"Nature"},{"key":"ref_65","first-page":"2476","article-title":"GATA4: Orchestrating Cardiac Development and Beyond","volume":"121","author":"Heuvelmans","year":"2025","journal-title":"Cardiovasc. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0076-6879(05)07030-8","article-title":"Regulation of Cell\u2013Cell Adhesion by Rap1","volume":"Volume 407","author":"Fujita","year":"2006","journal-title":"Methods in Enzymology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"35127","DOI":"10.1074\/jbc.M404917200","article-title":"Rap1 Regulates E-Cadherin-Mediated Cell-Cell Adhesion","volume":"279","author":"Price","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6690","DOI":"10.1128\/MCB.24.15.6690-6700.2004","article-title":"Rap1 Regulates the Formation of E-Cadherin-Based Cell-Cell Contacts","volume":"24","author":"Hogan","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular Mechanisms of Epithelial\u2013Mesenchymal Transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000113884","article-title":"Involvement of PI3K\/Akt Pathway in TGF-\u03b22-Mediated Epithelial Mesenchymal Transition in Human Lens Epithelial Cells","volume":"40","author":"Yao","year":"2008","journal-title":"Ophthalmic Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s42003-021-02003-6","article-title":"Av\u03b23 Integrin Induces Partial EMT Independent of TGF-\u03b2 Signaling","volume":"4","author":"Kariya","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1172\/JCI200523183","article-title":"Transcriptional Activation of Integrin B6 during the Epithelial-Mesenchymal Transition Defines a Novel Prognostic Indicator of Aggressive Colon Carcinoma","volume":"115","author":"Bates","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/bjc.2014.658","article-title":"Actin Cytoskeletal Control during Epithelial to Mesenchymal Transition: Focus on the Pancreas and Intestinal Tract","volume":"112","author":"Morris","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22164","DOI":"10.1038\/s41598-023-48279-y","article-title":"Morphological and Cytoskeleton Changes in Cells after EMT","volume":"13","author":"Nurmagambetova","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"41197","DOI":"10.1038\/s41598-025-24980-y","article-title":"Revealing the Complexity of the Epicardial Secretome","volume":"15","author":"Oliveira","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/(SICI)1097-0177(199903)214:3<229::AID-AJA6>3.0.CO;2-S","article-title":"The LIM Protein, CRP1, Is a Smooth Muscle Marker","volume":"214","author":"Henderson","year":"1999","journal-title":"Dev. Dyn."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"661","DOI":"10.2174\/1574888X15666200219105448","article-title":"Cardiac Repair: The Intricate Crosstalk between the Epicardium and the Myocardium","volume":"15","author":"Pellegrini","year":"2020","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1152\/physiolgenomics.00036.2019","article-title":"Transcriptional Sex and Regional Differences in Paired Human Atrial and Ventricular Cardiac Biopsies Collected in Vivo","volume":"52","author":"Synnergren","year":"2020","journal-title":"Physiol. Genom."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"13919","DOI":"10.1038\/s41598-018-32154-2","article-title":"Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles","volume":"8","author":"Johnson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_80","first-page":"e238334","article-title":"A Comprehensive Review of Atrial Infarction","volume":"51","author":"Grosso","year":"2024","journal-title":"Tex. Heart Inst. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/PAF.0b013e3181c14f81","article-title":"Left Atrial Infarction: A Case Report and Review of the Literature","volume":"31","author":"Rose","year":"2010","journal-title":"Am. J. Forensic Med. Pathol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1313\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:29:29Z","timestamp":1785115769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":81,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15141313"],"URL":"https:\/\/doi.org\/10.3390\/cells15141313","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}