Galectin-1 Improves Sarcolemma Repair and Decreases Inflammatory Response in LGMD2B Models


Translational Research

Poster Number: 40


Pam Van Ry , Mary Vallecillo-Zúniga , Mattew Rathgeber MSc, Daniel Poulson , Spencer Hayes , Jacob Luddington , Hailie Gill , Matthew Teynor , Braden Kartchner , Jonard Valdoz , Ashley Chang , Caleb Stowell , Connie Arthur PhD, Sean Stowell MD, PhD


1. Brigham Young University, 2. Brigham Young University, 3. BYU, 4. Brigham Young Univeristy, 5. BYU, 6. Brigham Young University, 7. Brigham Young University, 8. Brigham Young University, 9. Brigham Young University, 10. Brigham Young University, 11. Brigham Young University, 12. Brigham Young University, 13. Emory University, 14. Harvard Medical School

Background: 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. Galectin-1 (Gal-1) is a galactoside-binding protein capable of stabilizing the sarcolemma by increasing levels of ECM proteins. Gal-1 has been proven to improve muscle repair capacity in Duchenne muscular dystrophy (DMD) models resulting in healthier muscle fibers.
Objective: We hypothesize that galectin-1 will increase membrane repair capacity, myogenic potential, and decrease inflammation in LGMD2B models. To test this hypothesis, we used recombinant human galectin-1 (rHsGal-1) to treat dysferlin-deficient models.
Results: We found that rHsGal-1 treatment for a 48-72h period promotes myogenic maturation with enhanced size, myotube alignment, and membrane repair capacity in both dysferlin-deficient myotubes and myofibers. In vitro, explant myofiber and multiple in vivo rHsGal-1 treatment studies show an increased membrane repair capacity in LGMD2B models. Improvements in membrane repair after only a 10min rHsGal-1 in vitro treatment suggests mechanical stabilization of membrane due to interaction with glycosylated membrane bound, ECM or yet to be identified ligands through the CRD domain of Gal-1. rHsGal-l significantly reduces inflammation through the canonical NF-κB pathway. A one-week treatment with Gal-1 in dysferlin-null mice resulted in decreased inflammatory macrophages (M1) and an increase in anti-inflammatory macrophages (M2). After a one-month treatment with Gal-1, M1 macrophages remained reduced, although the M2 population also returned to saline-treated levels. The levels of p50 and p65 in muscles were also reduced during the one- month treatment.
Conclusions: Together our novel results reveal Gal-1 remediates disease pathologies in LGMD2B through changes in integral myogenic protein expression, mechanical membrane stabilization, immune modulation, and reducing canonical NF-κB inflammation.