GSK3β inhibition and canonical Wnt signaling in mice hearts after myocardial ischemic damage
| Autor: | Badimon, Lina, Casaní, Laura, Camino-López, S, Juan-Babot, Oriol, Borrell-Pages, Maria, Universitat Autònoma de Barcelona |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Critical Care and Emergency Medicine
Pyridines Protein Expression Myocardial Ischemia Myocardial Infarction Gene Expression 030204 cardiovascular system & hematology Biochemistry Mice 0302 clinical medicine Cell Signaling Gene expression Medicine and Health Sciences Myocardial infarction Phosphorylation Post-Translational Modification Wnt Signaling Pathway WNT Signaling Cascade Mice Knockout Multidisciplinary Wnt signaling pathway LRP5 Heart Signaling Cascades Low Density Lipoprotein Receptor-Related Protein-5 030220 oncology & carcinogenesis Medicine Signal transduction Anatomy Research Article Signal Transduction Signal Inhibition Science Cardiology Research and Analysis Methods 03 medical and health sciences medicine Genetics Gene Expression and Vector Techniques Animals Molecular Biology Techniques Gene Protein Kinase Inhibitors Molecular Biology Molecular Biology Assays and Analysis Techniques Glycogen Synthase Kinase 3 beta business.industry Myocardium Biology and Life Sciences Proteins Cell Biology medicine.disease Mice Inbred C57BL Pyrimidines Heart failure Reperfusion Cancer research Cardiovascular Anatomy business |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona PLoS ONE PLoS ONE, Vol 14, Iss 6, p e0218098 (2019) |
| Popis: | Altres ajuts: This work was supported by the Ministerio de Ciencia e Innovación (to LB); the Instituto de Salud Carlos III (to LB and to MBP); the Generalitat of Catalunya-Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat (to LB); the Fundacion Investigación Cardiovascular to LB, and the Spanish Society of Cardiology (SEC2015 to MBP). Aims Myocardial infarction induces myocardial injury and tissue damage. During myocardial infarction strong cellular response is initiated to salvage the damaged tissues. This response is associated with the induction of different signaling pathways. Of these, the canonical Wnt signaling is increasingly important for its prosurvival cellular role, making it a good candidate for the search of new molecular targets to develop therapies to prevent heart failure in infarcted patients. Methods Herein we report that GSK3β regulates the canonical Wnt signaling in C57Bl6 mice hearts. GSK3β is a canonical Wnt pathway inhibitor. Using GSK3β inhibitors and inducing myocardial injury (MI) in Lrp5 mice model we show that GSK3β phosphorylation levels regulate downstream canonical Wnt pathway genes in the ischemic heart. In the setting of MI, myocardial damage assessment usually correlates with functional and clinical outcomes. Therefore, we measured myocardial injury size in Wt and Lrp5 mice in the presence and absence of two different GSK3 inhibitors prior to MI. Myocardial injury was independent of GSK3 inhibitor treatments and GSK3β expression levels. Results These studies support a central role for GSK3β in the activation of the canonical Wnt pathway in the Wt heart. Although LRP5 is protective against myocardial injury, GSK3β expression levels do not regulate heart damage. |
| Databáze: | OpenAIRE |
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