TRPC1 modulates the PI3K/Akt pathway during myoblast differentiation and muscle regeneration
(2010) Day ED-PPP ULB — Location: ULB Brussels
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- Abstract
- We previously showed in vitro that calcium entry through Trpc1 ion channels regulates myoblast migration and differentiation. In the present work, we used primary cell cultures and isolated muscles from Trpc1-/- and Trpc1+/+ murine model to investigate the role of Trpc1 in myoblasts differentiation and in muscle regeneration. In these models, we studied regeneration consecutive to cardiotoxininduced muscle injury and observed a significant hypotrophy and a delayed regeneration in Trpc1-/- muscles consisting in smaller fibre size and increased proportion of centrally nucleated fibres. This was accompanied by a decreased expression of myogenic factors such as MyoD, Myf5 and myogenin, and of one of their target, the developmental Myosin Heavy Chain (MHCd). Consequently, muscle tension was systematically lower in muscles from Trpc1-/- mice. Importantly, the PI3K/Akt/mTOR/p70S6K pathway, which plays a crucial role in muscle growth and regeneration, was down regulated in regenerating Trpc1-/- muscles. Indeed, phosphorylation of both Akt and p70S6K proteins was decreased, as well as the activation of PI3K, the main upstream regulator of the Akt. This effect was independent of IGF expression. Akt phosphorylation was also reduced in Trpc1-/- primary myoblasts and in control myoblasts differentiated in the absence of extracellular Ca2+ or pre-treated with EGTA-AM or wortmannin, suggesting that the entry of Ca2+ through Trpc1 channels enhanced the activity of PI3K.
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Zanou, N., Schakman, O., Louis, P., & Gailly, P. (2010). TRPC1 modulates the PI3K/Akt pathway during myoblast differentiation and muscle regeneration. Day ED-PPP ULB, ULB Brussels. https://hdl.handle.net/2078.5/76924