FIGURE 1.

A schematic highlighting the overall beneficial and detrimental actions of EGFR/ErbB receptors and their downstream signaling effectors in the diabetic heart. It appears that all four EGFR/ErbB receptors are necessary for the development of the heart during embryogenesis and beneficial for the proper functioning of the adult heart including a key role in maintenance of cardiac contractility. EGFR/ErbB2 signaling is also essential for normal cardiomyocyte function. Acute stimulation of EGFR/ErbB receptor signaling is also essential for activation of salvage pathways and cardiac recovery following I/R injury. In addition to these beneficial actions, EGFR/ErbB receptor signaling can also have detrimental outcomes. Persistent or chronic upregulation of EGFR/ErbB receptor signaling has been involved in the development of cardiac dysfunction and pathologies including fibrosis, remodelling and hypertrophy. Several key downstream effectors are involved in mediating both actions with some notable overlaps such as AKT and ERK1/2 (highlighted)- implying that they too can have dual actions depending on the pathophysiological context akin to the role of their upstream EGFR/ErbB receptors (see main text for further details and references).