Ambient Hypoxia Differentially Impacts Thrombospondin-1 and Thrombospondin-4 in Differentiated Murine Myotubes

Abstract

Skeletal muscle microvasculature responds to stimuli with great plasticity through angioadaptation which itself is tightly regulated by a balance of pro- and antiangiogenic factors. THBS-1 has been established as the key antiangiogenic factor in skeletal muscle, and its homologue, THBS-4, has recently been identified as a proangiogenic factor in tissue other than skeletal muscle. Hypoxia has been shown to be a principal component of exercise, a potent angiogenic stimulus, yet its impact on THBS-1 and THBS-4 in myotubes has rarely been examined. My project aimed to investigate the impact of hypoxia on THBS-1 and THBS-4 in differentiated murine myotubes. The findings suggest that 1) myotubes are a source of THBS-1, 2) hypoxia greatly reduces THBS-1 and THBS-4 intracellular expression after 24 hours, and 3) hypoxia differentially impacts THBS-1 and THBS-4 in their protein stability and secretion. My research concludes that hypoxia differentially impacts THBS-1 and THBS-4 in myotubes.