Defining the roles of insulin-like growth factor and p38 MAP kinase signaling pathways in muscle differentiation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 88-108-GHRH, GH & IGF Biology & Signaling
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-100
Samantha Gardner*, Magdalena Anguiano, Sean Gross and Peter S Rotwein
Oregon Health & Science University, Portland, OR
Skeletal muscle formation requires the co-operation of environmentally controlled growth factor signaling pathways with genetically determined transcriptional programs. Muscle differentiation may be separated into several phases: myoblasts initially proliferate, then withdraw from the cell cycle and express muscle proteins, which direct elongation, alignment, and fusion of myocytes to form primary myotubes; finally, additional myocytes fuse with the nascent myotubes to form multinucleated myofibers. Although much progress has been made in elucidating the signaling pathways involved in the early steps of muscle differentiation, the molecular mechanisms controlling myocyte fusion have remained largely unknown. Here we have examined the interplay of insulin-like growth factor (IGF) and p38 MAP kinase signaling pathways in myotube formation. Chemical inhibitors of p38 activity (SB202190 and BIRB796) dose-dependently inhibited biochemical and morphological differentiation of the C2 myoblast cell line. Addition of IGF-I (R3-IGF-I, [1 nM]) in the presence of the p38 inhibitors stimulated robust expression of muscle proteins, and myocyte elongation and alignment; however, little fusion occurred until after the p38 inhibitor was removed. Taken together, these results show that although both IGF-activated and p38-mediated pathways are required for normal muscle differentiation, the actions of p38 dominantly control fusion to generate multinucleated myotubes. Our observations provide a testable means to identify the key regulatory molecules involved in myofiber formation during the later stages of muscle differentiation.

Nothing to Disclose: SG, MA, SG, PSR

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