Exploring lipin1 as a promising therapeutic target for the treatment of Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a progressive and devastating muscle disease, resulting from the absence of dystrophin. This leads to cell membrane instability, susceptibility to contraction-induced muscle damage, subsequent muscle degeneration, and eventually disability and early death of patients. Currently, there is no cure for DMD.

Automated Image Analysis Pipeline Development to Monitor Disease Progression in Muscular Dystrophy Using Cell Profiler.

Muscular dystrophies are inherited disorders that are characterized by progressive muscle degeneration. These disorders are caused by mutations in the genes encoding structural elements within the muscle, which leads to increased vulnerability to mechanical stress and sarcolemma damage. Although myofibers have the capacity to regenerate, the newly formed myofibers still harbor genetic mutation, which induces continuous cycles of muscle fiber death and regeneration.

Lipin1 plays complementary roles in myofibre stability and regeneration in dystrophic muscles.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by dystrophin mutations, leading to the loss of sarcolemmal integrity, and resulting in progressive myofibre necrosis and impaired muscle function. Our previous studies suggest that lipin1 is important for skeletal muscle regeneration and myofibre integrity. Additionally, we discovered that mRNA expression levels of lipin1 were significantly reduced in skeletal muscle of DMD patients and the mdx mouse model.

Loss of membrane integrity drives myofiber death in lipin1-deficient skeletal muscle.

Mutations in lipin1 are suggested to be a common cause of massive rhabdomyolysis episodes in children; however, the molecular mechanisms involved in the regulation of myofiber death caused by the absence of lipin1 are not fully understood. Loss of membrane integrity is considered as an effective inducer of cell death in muscular dystrophy. In this study, we utilized a mouse line with selective homozygous lipin1 deficiency in the skeletal muscle (Lipin1 ) to determine the role of compromised membrane integrity in the myofiber death in lipin1-deficient muscles.

Lipin1 is required for skeletal muscle development by regulating MEF2c and MyoD expression.

Key Points: Lipin1 is critical for skeletal muscle development. Lipin1 regulates MyoD and myocyte-specific enhancer factor 2C (MEF2c) expression via the protein kinase C (PKC)/histone deacetylase 5-mediated pathway. Inhibition of PKCμ activity suppresses myoblast differentiation by inhibiting MyoD and MEF2c expression.

Lipin-1 regulates Bnip3-mediated mitophagy in glycolytic muscle.

Autophagy of mitochondria (mitophagy) is essential for maintaining muscle mass and healthy skeletal muscle. Patients with heritable phosphatidic acid phosphatase lipin-1-null mutations present with severe rhabdomyolysis and muscle atrophy in glycolytic muscle fibers, which are accompanied with mitochondrial aggregates and reduced mitochondrial cytochrome c oxidase activity. However, the underlying mechanisms leading to muscle atrophy as a result of lipin-1 deficiency are still not clear.