P.19.9 Gαi2 signaling is required for skeletal muscle regeneration and for satellite cell differentiation

Abstract

We have previously shown that expression of a constitutively active mutant of the a subunit of the heterotrimeric G α i2 protein, G α i2 (Q205L), is sufficient to induce skeletal muscle hypertrophy, myoblast differentiation and to accelerate muscle regeneration. To elucidate the requirement of G α i2 in skeletal muscle growth and regeneration we have analyzed mice genetically deficient in G α i2. We show that G α i2 KO mice display decreased lean body mass, reduced muscle size and impaired skeletal muscle regeneration after cardiotoxin-induced injury. In addition, G α i2 expression is increased during skeletal muscle regeneration after cardiotoxin injection. ShRNA-mediated knock down of G α i2 in satellite cell leads to reduced expression of the activation markers Pax3 and Pax7, as well as defective satellite cell proliferation, fusion and differentiation ex vivo. The impaired differentiation is consistent with the observation that the myogenic regulatory factors MyoD and Myf5 are down-regulated upon knock down of G α i2. Interestingly, the expression of miR-1 and miR-206, two microRNAs that have been shown to regulate satellite cell proliferation and differentiation, is upregulated by a constitutively active mutant of G α i2. These findings provide evidence for the requirement of G α i2 in satellite cell differentiation ex vivo and for skeletal muscle regeneration in vivo.