A New Method of Myostatin Inhibition in Mice via Oral Administration of Lactobacillus casei Expressing Modified Myostatin Protein, BLS-M22.
Dong Kyung SungHyeongseop KimSang Eon ParkJiwon LeeJu-A KimYoung-Chul ParkHong Bae JeonJong Wook ChangJeehun LeePublished in: International journal of molecular sciences (2022)
Myostatin is a member of the transforming growth factor-beta superfamily and is an endogenous negative regulator of muscle growth. This study aimed to determine whether an oral administration of Lactobacillus casei expressing modified human myostatin (BLS-M22) could elicit sufficient levels of myostatin-specific antibody and improve the dystrophic features of an animal model of Duchenne muscular dystrophy (DMD; mdx mouse). BLS-M22 is a recombinant L. casei engineered to harbor the pKV vector and poly-gamma-glutamic acid gene linked to a modified human myostatin gene. Serological analysis showed that anti-myostatin IgG titers were significantly increased, and serum creatine kinase was significantly reduced in the BLS-M22-treated mdx mice compared to the control mice. In addition, treatment of BLS-M22 resulted in a significant increase in body weight and motor function (Rotarod behavior test). Histological analysis showed an improvement in the dystrophic features (fibrosis and muscle hypertrophy) of the mdx mice with the administration of BLS-M22. The circulating antibodies generated after BLS-M22 oral administration successfully lowered serum myostatin concentration. Myostatin blockade resulted in serological, histological, and functional improvements in mdx mice. Overall, the findings suggest the potential of BLS-M22 to treat DMD; however, further clinical trials are essential to ascertain its efficacy and safety in humans.
Keyphrases
- duchenne muscular dystrophy
- high fat diet induced
- transforming growth factor
- clinical trial
- endothelial cells
- body weight
- muscular dystrophy
- wild type
- genome wide
- epithelial mesenchymal transition
- type diabetes
- insulin resistance
- metabolic syndrome
- transcription factor
- randomized controlled trial
- adipose tissue
- signaling pathway
- climate change
- genome wide identification
- tyrosine kinase
- cell free