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Journal of Undergraduate Research

Keywords

IP-10, muscle regeneration, repair after injury, skeletal muscle stem cells

College

Life Sciences

Department

Exercise Sciences

Abstract

The repair and regeneration processes of skeletal muscle rely on the activation, proliferation and differentiation of skeletal muscle stem cells (satellite cells), which are necessary sources for muscle increase (hypertrophy) and regeneration (Stewart, 2006). A muscles ability to regenerate diminishes due to age or various diseases, such as muscular dystrophy (Mariol, 2001). Interventions aimed at altering the skeletal muscle environment to optimize muscle stem cell activity and regenerative processes represents a promising approach to enhance muscle regenerative capacity. Recent data from our lab has identified increased levels of the cytokine Interferon Gamma-Inducible Protein 10 (IP-10) during the muscle regenerative period following damage in human muscle (Hyldahl, 2014). IP-10 is primarily considered to function as a chemoattractant for monocytes and T lymphocytes, playing an important role in mediating physiological inflammatory responses. Additionally, it has been suggested that IP-10 may play a distinct role in vascular remodeling as it induced smooth muscle proliferation and migration following vascular injury (Wang, 1996). Currently, no biological functions of IP-10 in the repair and regeneration processes of skeletal muscle have been reported. I collected data showing that introducing IP-10 in vitro increased both proliferation and differentiation of human primary myoblasts. With these data, we hypothesized that IP-10 plays a role in the proliferation and differentiation of muscle satellite cells in vivo. By utilizing a mouse model of IP-10 deficiency, we sought to determine how IP-10 contributes to the skeletal muscle regenerative process at various time points following a controlled injury. We hypothesized that the muscle fiber (myofiber) cross-sectional area would remain significantly lower following muscle injury in IP-10 knockout mice. The cross-sectional area of myofibers exhibiting centralized nuclei provides insight into skeletal muscle structure and the progress of repair (Lee, 2013). We also hypothesized that IP-10 knockout mice will experience significantly lower rates of satellite cell proliferation following injury. Originally, we sought to measure proliferation by injecting the mice with EdU (5-ethynyl-2’-deoxyuridine) during treatment, a compound used to label the DNA of actively proliferating cells. However, in order to maximize the tissue sample for other uses, we decided that measurement of satellite cell proliferation should be done by staining fixed tissue for the satellite cell marker Pax7 (Seale, 2000)

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