Murine Double Minute-2 signaling pathway regulates exercise-induced angiogenesis in rodent skeletal muscle

骨骼肌占我们体重的40%以上，参与非常重要的生理功能，如身体运动或葡萄糖稳态。

Skeletal muscles represent more than 40% of our body weight and participate in very important physiological functions such as body mobility or glucose homeostasis. Blood vessels represent a key element of skeletal muscle function. With a remarkable plasticity, capillaries - our smallest blood vessels - ensure a good match between muscle blood perfusion capacities and the needs of our muscle cells in oxygen and nutrients. Physical exercise is a physiological situation that stimulates the formation of new capillaries in our skeletal muscles. This biological process, named angiogenesis, is tightly regulated by stimulatory and inhibitory molecular factors. We have recently demonstrated that a protein named Murine Double Minute-2 (Mdm2) was an important actor of muscle angiogenesis in response to running exercise. However, the molecular mechanisms through which Mdm2 exert its pro-angiogenic action remain unknown. Our research program will pursue our initial work on Mdm2. We now aim to identify the upstream signaling pathways that regulate Mdm2 activity and expression in response to exercise; and we will also focus on the downstream pathways through which Mdm2 mediates its pro-angiogenic action. Our project will represent an innovative and important contribution in the field of muscle physiology research since we describe here a novel role for Mdm2 in muscle tissue. This will improve our understanding of the cellular and molecular mechanisms that regulate vascular adaptability in skeletal muscle. This might also be of interest in the context of several diseases that affect the muscle vasculature (diabetes, chronic heart failure).