An Update on the Multifaceted Roles of STAT3 in the Heart
- 1Faculty of Sciences, Doctoral School of Sciences and Technology, Laboratory of Experimental and Clinical Pharmacology, Lebanese University, Lebanon
- 2Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, United States
- 3CarMeN Laboratory, INSERM 1060, INRA 1397, Université Claude Bernard Lyon 1, France
- 4CarMeN Laboratory, IHU Opera, INSERM U1060, Université Claude Bernard Lyon 1, France
Signal transducer and activator of transcription 3 (STAT3) is a signaling molecule and transcription factor that plays important protective roles in the heart. The protection mediated by STAT3 is attributed to its genomic actions as a transcription factor and other non-genomic roles targeting mitochondrial function and autophagy. As a transcription factor, STAT3 upregulates genes that are anti-oxidative, anti-apoptotic, and pro-angiogenic, but suppresses anti-inflammatory and anti-fibrotic genes. Its suppressive effects on gene expression are achieved through competing with other transcription factors or cofactors. STAT3 is also linked to the modification of mRNA expression profiles in cardiac cells by inhibiting or inducing miRNA. In addition to these genomic roles, STAT3 is suggested to function protectively in mitochondria, where it regulates ROS production, in part by regulating the activities of the electron transport chain complexes, although our recent evidence calls this role into question. Nonetheless, STAT3 is a key player known to be activated in the cardioprotective ischemic conditioning protocols. Through these varied roles, STAT3 participates in various mechanisms that contribute to cardioprotection against different heart pathologies, including myocardial infarction, hypertrophy, diabetic cardiomyopathy, and peripartum cardiomyopathy. Understanding how STAT3 is involved in the protective mechanisms against these different cardiac pathologies could lead to novel therapeutic strategies to treat them.
Keywords: STAT3 (signal transducer and activator of transcription 3), Cardioprotection, Cardiac pathologies, Myocardial Infarction, genomic functions
Received: 14 Jul 2019;
Accepted: 07 Oct 2019.
Copyright: © 2019 Harhous, Booz, Ovize, Bidaux and Kurdi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Gabriel Bidaux, Université Claude Bernard Lyon 1, CarMeN Laboratory, IHU Opera, INSERM U1060, Lyon, 69622, Rhône-Alpes, France, firstname.lastname@example.org
Prof. Mazen Kurdi, Lebanese University, Faculty of Sciences, Doctoral School of Sciences and Technology, Laboratory of Experimental and Clinical Pharmacology, Beirut, 1107 2020, Lebanon, email@example.com