Understanding Interorgan Crosstalk at the Molecular Level upon Exercise
Secretome of Bone and Muscle upon Exercise
Bone and muscle are essential components of performing exercise and are directly affected by exercise. Furthermore, these organs are not only altered it-selves as a response to exercise, but also affect physiological functions of body systems through inter-organ crosstalk. According to a recent study by several researchers, Myokines, hormones secreted by muscles, are responsible for much of this crosstalk. However, the myokines produced by exercise have not been fully identified yet, so we will screen the myokines to perform inter-organ signaling upon exercise.
In addition, we will discover how bones also affect other body organs by exercise. Bones also secrete hormones (osteokines) to regulate bone remodeling and to act as an endocrine organ that is secreted into the blood and affects other organs. However, it is not yet known what kinds of osteokines are produced by exercise and how they are controlled, so we are going to reveal the osteokines secreted upon exercise.
We plan to identify bone/muscle-secreted factors in live mice using iSLET (in situ Secretory Protein Labeling via ER-anchored TurboID) method. These iSLET mice express Sec61B-TurboID that can biotinylate the proteins on the ER membrane of the cell, specifically inbone or muscle. Next, biotin-labeled secretory proteins are collected from the plasma and then can be detected by MS analysis. Hormone metabolites responsive to exercise also can be discovered using tracking stable isotope-labeled compounds.
Understanding Microgravity Effect on Muscle and Bone
Mechanical stimuli is the major outcome of exercise. As known, the lack of mechanical stimuli such as microgravity condition causes bone and muscle loss, which has been well observed in the space. Preventing bone and muscle loss in space is a critical issue to solve to meet the growing public-interest in space exploration and for disease diagnosis or treatment. We will utilize the random positioning machine to mimic microgravity condition and test how muscle and bone cells respond to microgravity. The secreted factors from bone and muscle will be applied to therapeutic approaches to recover bone and muscle from microgravity-induced loss.