Transforming growth factor β (TGF-β) is a multifunctional cytokine with fibrogenic properties. Previous studies demonstrated that Phosphatidylinositol 3-Kinase (PI3K)/Akt/ mammalian target of Ramycin (mTOR), a non-Smad TGF-β pathway, plays an important role in the fibrotic pathogenesis of different organs such as the lung, kidney, skin and liver. However, the role of PI3k-Akt pathway in fibrosis in injured skeletal muscle is still unclear. In this study, we determined the fibrotic role of PI3K-Akt pathway in injured skeletal muscle. We established a mouse model for acute muscle contusion. Western blotting analysis showed that TGF-β, phosphorylated Akt and phosphorylated mTOR were increased in muscles after acute contusion, which indicated that the PI3K-Akt- mTOR pathway was activated in skeletal muscle after acute contusion. The pathway was inhibited by a PI3K inhibitor, LY294002. Moreover, the expression of fibrosis markers vimentin, α SMA and collagen I and the area of scar decreased in injured skeletal muscle after PI3K pathway was blocked. The muscle function improved in terms of both fast-twitch and tetanic strength after PI3K/Akt pathway was inhibited in injured skeletal muscle. In conclusion, activation of PI3K-Akt-mTOR pathway might promote collagen production and scar formation in the acute contused skeletal muscle. Blocking of PI3K-Akt-mTOR pathway could improve the function of injured skeletal muscle.

Studies have shown that functional ankle instability can result in prolonged muscle reaction time. However, the deficit in muscle reaction time in patients with mechanical ankle instability (MAI) and the effect of lateral ankle ligament repair on muscle reaction time are unclear. The purpose of this study was to identify the deficit in muscle reaction time, and to evaluate the role of lateral ligament repair in improving muscle reaction time in MAI patients. Sixteen MAI patients diagnosed with lateral ankle ligament tears by ultrasonography and magnetic resonance imaging underwent arthroscopic debridement and open lateral ankle ligament repair with a modified Broström procedure. One day before the operation, reaction times of the tibialis anterior and peroneus longus muscles were recorded following sudden inversion perturbation while walking on a custom walkway, and anterior drawer test (ADT) and American Orthopaedic Foot and Ankle Society (AOFAS) scale score were evaluated. Six months postoperatively, muscle reaction time, ADT and AOFAS scale score were reevaluated, and muscle reaction times in 15 healthy controls were also recorded. Preoperatively, the affected ankles in the MAI group had significantly delayed tibialis anterior and peroneus longus muscles reaction times compared with controls. Six months after the operation, median AOFAS scale scores were significantly greater than preoperatively, and ADT was negative in the MAI group. However, the affected ankles in the MAI group showed no difference in muscle reaction time compared with preoperative values. MAI patients had prolonged muscle reaction time. The modified Broström procedure produced satisfactory clinical outcomes in MAI patients, but did not shorten reaction times of the tibialis anterior and peroneus longus muscles.