Myogenic Akt Signaling Upregulates the Utrophin-Glycoprotein Complex and Promotes Sarcolemma Stability in Muscular Dystrophy
Peter, Angela K.
Ko, Christopher Y.
Kim, Michelle H.
Crosbie, Rachelle H.
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Citation (published version)Peter, Angela K., Christopher Y. Ko, Michelle H. Kim, Nigel Hsu, Noriyuki Ouchi, Suhn Rhie, Yasuhiro Izumiya, Ling Zeng, Kenneth Walsh, Rachelle H. Crosbie. "Myogenic Akt Signaling Upregulates the Utrophin-Glycoprotein Complex and Promotes Sarcolemma Stability in Muscular Dystrophy" Human Molecular Genetics 18(2): 318-327. (2008)
Duchenne muscular dystrophy is caused by dystrophin mutations that lead to structural instability of the sarcolemma membrane, myofiber degeneration/regeneration and progressive muscle wasting. Here we show that myogenic Akt signaling in mouse models of dystrophy promotes increased expression of utrophin, which replaces the function of dystrophin thereby preventing sarcolemma damage and muscle wasting. In contrast to previous suggestions that increased Akt in dystrophy was a secondary consequence of pathology, our findings demonstrate a pivotal role for this signaling pathway such that modulation of Akt can significantly affect disease outcome by amplification of existing, physiological compensatory mechanisms.