TP B2 The role of miR-221/222 in EGFR-mediated changes in the cardiovascular system
The EGFR is a ubiquitously expressed receptor tyrosine kinase that can be activated by different ligands like EGF and/or is trans-activated by a variety of stimuli including G-protein-coupled receptors and cellular stress; thus, the EGFR is an important interconnection. In the cardiovascular system, an association of EGFR with impaired vascular and cardiac function and parainflammatory remodeling processes has been made based on clinical and experimental data of pharmacological EGFR inhibitors and mice with reduced EGFR tyrosine kinase activity. These findings remain partially contradictory and the underlying molecular mechanisms are not completely understood.
In recent years, miRNAs have been implicated in the regulation of pathological cardiac and vascular phenotypes, and the EGFR signaling cascade has been suggested as a regulator of miR expression. One of the most prominent miR clusters associated with cardiovascular homeostasis and pathology is miR-221/222. These miRs also show altered expression in the aorta and heart of mice with targeted deletion of EGFR, suggesting an involvement of these miRs in EGFR s role in the cardiovascular system.
Aim of the current project is to explore the mechanisms and role of EGFR for cardiovascular miR-221/222 deregulation and to investigate the cellular and functional consequences of EGFR-dependent miR-221/222 deregulation.