Treatment with galectin-1 improves myogenic potential and membrane repair in dysferlin-deficient models

• Published in: PloS one 2020-09, Vol.15 (9), p.e0238441-e0238441
• Main Authors: Vallecillo-Zúniga, Mary L., Rathgeber, Matthew F., Poulson, P. Daniel, Hayes, Spencer, Luddington, Jacob S., Gill, Hailie N., Teynor, Matthew, Kartchner, Braden C., Valdoz, Jonard, Stowell, Caleb, Markham, Ashley R., Arthur, Connie, Stowell, Sean, Van Ry, Pam M.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biology and Life Sciences; Blood banks; Calcium; Carbohydrates; Cloning; Deoxyribonucleic acid; DNA; Domains; Dystrophy; Engineering and Technology; Extracellular matrix; Galectin-1; Hypotheses; Laboratories; Maturation; Membrane proteins; Membranes; Muscles; Muscular dystrophy; Mutation; Myoblasts; Myogenesis; Myotubes; Proteins; Repair; Research and Analysis Methods; Stabilization
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0238441

Limb-girdle muscular dystrophy type 2B (LGMD2B) is caused by mutations in the dysferlin gene, resulting in non-functional dysferlin, a key protein found in muscle membrane. Treatment options available for patients are chiefly palliative in nature and focus on maintaining ambulation. Our hypothesis is that galectin-1 (Gal-1), a soluble carbohydrate binding protein, increases membrane repair capacity and myogenic potential of dysferlin-deficient muscle cells and muscle fibers. To test this hypothesis, we used recombinant human galectin-1 (rHsGal-1) to treat dysferlin-deficient models. We show that rHsGal-1 treatments of 48 h-72 h promotes myogenic maturation as indicated through improvements in size, myotube alignment, myoblast migration, and membrane repair capacity in dysferlin-deficient myotubes and myofibers. Furthermore, increased membrane repair capacity of dysferlin-deficient myotubes, independent of increased myogenic maturation is apparent and co-localizes on the membrane of myotubes after a brief 10min treatment with labeled rHsGal-1. We show the carbohydrate recognition domain of Gal-1 is necessary for observed membrane repair. Improvements in membrane repair after only a 10 min rHsGal-1treatment suggest mechanical stabilization of the membrane due to interaction with glycosylated membrane bound, ECM or yet to be identified ligands through the CDR domain of Gal-1. rHsGal-1 shows calcium-independent membrane repair in dysferlin-deficient and wild-type myotubes and myofibers. Together our novel results reveal Gal-1 mediates disease pathologies through both changes in integral myogenic protein expression and mechanical membrane stabilization.