{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:44:49Z","timestamp":1793148289941,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>How canonical Wnt\/\u03b2-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>We investigated canonical Wnt\/\u03b2-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin\u2013related cardiomyopathy. Our data demonstrated that canonical Wnt\/\u03b2-catenin signaling was activated through nuclear accumulation of \u03b2-catenin in idiopathic dilated cardiomyopathy, ischemic heart disease, and murine desmin\u2013related cardiomyopathy when compared with nonfailing controls and transcription factor 7-like 2 (TCF7L2) was the main \u03b2-catenin partner of the T-cell factor (TCF) family in adult hearts. We further revealed that c-Myc mRNA and protein levels were significantly elevated in failing hearts by real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. Immunoprecipitation and confocal microscopy further showed that \u03b2-catenin interacted and colocalized with TCF7L2. More importantly, chromatin immunoprecipitation confirmed that \u03b2-catenin and TCF7L2 were recruited to the regulatory elements of c-Myc. This recruitment was associated with increased histone H3 acetylation and transcriptional upregulation of c-Myc. With lentiviral infection, TCF7L2 overexpression increased c-Myc expression and cardiomyocyte size, whereas shRNA-mediated knockdown of TCF7L2 suppressed c-Myc expression and cardiomyocyte growth in cultured neonatal rat cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>This study indicates that TCF7L2 mediates canonic Wnt\/\u03b2-catenin signaling and c-Myc upregulation during abnormal cardiac remodeling in heart failure and suppression of Wnt\/\u03b2-catenin to c-Myc axis can be explored for preventing and treating heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.116.003010","type":"journal-article","created":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T13:26:21Z","timestamp":1465997181000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Transcription Factor 7-like 2 Mediates Canonical Wnt\/\u03b2-Catenin Signaling and c-Myc Upregulation in Heart Failure"],"prefix":"10.1161","volume":"9","author":[{"given":"Ning","family":"Hou","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Guangzhou Medical University, China (N.H.); Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY (N.H., B.Y., X.L., F.L.); Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardiovascular Research Center, Minneapolis (B.Y., F.L.); Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia (K.B.M.); Department of Pathology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Ye","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Guangzhou Medical University, China (N.H.); Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY (N.H., B.Y., X.L., F.L.); Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardiovascular Research Center, Minneapolis (B.Y., F.L.); Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia (K.B.M.); Department of Pathology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Guangzhou Medical University, China (N.H.); Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY (N.H., B.Y., X.L., F.L.); Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardiovascular Research Center, Minneapolis (B.Y., F.L.); Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia (K.B.M.); Department of Pathology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Margulies","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Guangzhou Medical University, China (N.H.); Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY (N.H., B.Y., X.L., F.L.); Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardiovascular Research Center, Minneapolis (B.Y., F.L.); Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia (K.B.M.); Department of Pathology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodong","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Guangzhou Medical University, China (N.H.); Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY (N.H., B.Y., X.L., F.L.); Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardiovascular Research Center, Minneapolis (B.Y., F.L.); Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia (K.B.M.); Department of Pathology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Guangzhou Medical University, China (N.H.); Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY (N.H., B.Y., X.L., F.L.); Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardiovascular Research Center, Minneapolis (B.Y., F.L.); Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia (K.B.M.); Department of 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