FHL1 reduces muscle degeneration in dystrophin-deficient mdx mice through the sarcolemmal recruitment of utrophin

Abstract

Duchenne muscular dystrophy (DMD) is caused by dystrophin gene mutations, resulting in loss of dystrophin from the sarcolemma. Utrophin is a therapeutic target for DMD due to its functional compensation for dystrophin, by forming the protective utrophin–glycoprotein complex (UGC) at the sarcolemma. In adult muscle fibres utrophin localizes to the neuromuscular junction, therefore the challenge is to identify factors which increase utrophin expression and sarcolemmal recruitment. Calcineurin/NFATc1 is a utrophin regulatory pathway and we reported that FHL1 coactivates NFATc1. We crossed our skeletal muscle FHL1 transgenic mice with the mdx model of DMD. FHL1 ameliorated degeneration in multip..