Skeletal muscle growth is associated with, and dependent upon, the addition of newly formed nuclei via the fusion of myoblasts to the myotube. Thus, the capability of muscle fibers to grow is critically dependent on myoblast proliferation and/or survival. Cyclic mechanical stretch stimulates proliferation in a variety of cell types (9, 15). Therefore, we will utilize cyclic mechanical stretch of cultured myoblasts to identify signal transduction pathways that potentially regulate myoblast proliferation and/or survival. This proposal has three overall goals: (1) to determine the influence of stretch on myoblast proliferation and/or survival; (2) to identify the role of calcineurin (CaN) and its downstream effector Nuclear Factor of Activated T Cells (NFAT) in regulating myoblast proliferation and/or survival secondary to cyclic mechanical stretch; and, (3) to elucidate a potential role for Vascular Endothelial Growth Factor (VEGF) on myoblast proliferation and/or survival following cyclic mechanical stretch. Understanding the molecular mechanisms that regulate muscle growth is important for developing effective pharmacologic or genetic therapies to combat the number of clinical conditions associated with muscle atrophy.
|Otis, Jeffrey S; Brown, Lou Ann S; Guidot, David M (2007) Oxidant-induced atrogin-1 and transforming growth factor-beta1 precede alcohol-related myopathy in rats. Muscle Nerve 36:842-8|
|Otis, Jeffrey S; Lees, Simon J; Williams, Jay H (2007) Functional overload attenuates plantaris atrophy in tumor-bearing rats. BMC Cancer 7:146|
|Otis, Jeffrey S; Burkholder, Thomas J; Pavlath, Grace K (2005) Stretch-induced myoblast proliferation is dependent on the COX2 pathway. Exp Cell Res 310:417-25|