The effect of optn in muscle atrophy
Skeletal muscle atrophy, a disease seriously affects the quality of life and prognosis of patients, is caused by various clinical conditions, yet its underlying mechanism remains elusive. Here, we show that OPTN is highly associated with muscle atrophy. Optn knockdown (KD) induces muscle atrophy in mice. In contrast, AAV-mediated Optn overexpression protects against dexamethasone (Dex) induced muscle atrophy in mice. Optn KD significantly decreased phosphorylation levels of PI3 Kinase p85, AKT and FOXO3A in TA muscle of mice, while pharmacological activation of PI3K-AKT signaling pathway rescues Optn KD-induced muscle atrophy. These results indicate that PI3K-AKT signaling pathway plays an indispensable role in OPTN-mediated muscle atrophy. Mechanistically, we further identified JUP, a key effector of PI3K-AKT signaling pathway, as the interacting partner of OPTN. OPTN coordinates the interaction of PI3 Kinase p85 and JUP in skeletal muscle, promoting the activation of PI3K-AKT signaling pathway. Therapeutically, we show that OPTN attenuates Dex-induced muscle atrophy in a JUP-dependent manner. Together, our study delineates the novel role of OPTN as a potential regulator of muscle atrophy, unveiling the mechanism that OPTN-JUP axis mediates the transduction of PI3K-AKT signaling pathway during muscle atrophy. These results discover the innovative therapeutic perspectives for muscle atrophy.