Peter Angela K, Ko Christopher Y, Kim Michelle H, Hsu Nigel, Ouchi Noriyuki, Rhie Suhn, Izumiya Yasuhiro, Zeng Ling, Walsh Kenneth, Crosbie Rachelle H
Department of Physiological Science, University of California, Los Angeles, CA 90095, USA.
Hum Mol Genet. 2009 Jan 15;18(2):318-27. doi: 10.1093/hmg/ddn358. Epub 2008 Nov 4.
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.
杜兴氏肌营养不良症是由肌营养不良蛋白突变引起的，这些突变导致肌膜结构不稳定、肌纤维变性/再生以及进行性肌肉萎缩。我们在此表明，在肌营养不良症小鼠模型中，肌源性Akt信号传导可促进肌养蛋白表达增加，肌养蛋白可替代肌营养不良蛋白的功能，从而防止肌膜损伤和肌肉萎缩。与之前认为肌营养不良症中Akt增加是病理的次要后果的观点相反，我们的研究结果证明了该信号通路的关键作用，即通过放大现有的生理补偿机制，调节Akt可显著影响疾病结局。
