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Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B
- Source :
- Cells, Volume 10, Issue 11, Cells, Vol 10, Iss 3210, p 3210 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- Two of the main pathologies characterizing dysferlinopathies are disrupted muscle membrane repair and chronic inflammation, which lead to symptoms of muscle weakness and wasting. Here, we used recombinant human Galectin-1 (rHsGal-1) as a therapeutic for LGMD2B mouse and human models. Various redox and multimerization states of Gal-1 show that rHsGal-1 is the most effective form in both increasing muscle repair and decreasing inflammation, due to its monomer-dimer equilibrium. Dose-response testing shows an effective 25-fold safety profile between 0.54 and 13.5 mg/kg rHsGal-1 in Bla/J mice. Mice treated weekly with rHsGal-1 showed downregulation of canonical NF-κB inflammation markers, decreased muscle fat deposition, upregulated anti-inflammatory cytokines, increased membrane repair, and increased functional movement compared to non-treated mice. Gal-1 treatment also resulted in a positive self-upregulation loop of increased endogenous Gal-1 expression independent of NF-κB activation. A similar reduction in disease pathologies in patient-derived human cells demonstrates the therapeutic potential of Gal-1 in LGMD2B patients.
- Subjects :
- Male
muscular dystrophy
Galectin 1
QH301-705.5
Muscle Fibers, Skeletal
Endogeny
Inflammation
Article
law.invention
NF-ĸB
Mice
Downregulation and upregulation
law
Galectin-1
Medicine
Animals
Humans
Muscular dystrophy
Biology (General)
Wasting
Dysferlin
Membranes
business.industry
NF-kappa B
Muscle weakness
General Medicine
medicine.disease
Recombinant Proteins
cytokines
Muscular Dystrophies, Limb-Girdle
membrane repair
inflammation
Cancer research
Recombinant DNA
medicine.symptom
Protein Multimerization
business
Biomarkers
Signal Transduction
LGMD2B
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....e0d4d3f7638b2a6da765b7aea93af0f5
- Full Text :
- https://doi.org/10.3390/cells10113210