High mobility group box 1 (HMGB1) is a potential disease biomarker in cell and mouse models of Duchenne muscular dystrophy. Biol Open 2024 Sep 15;13(9)
Date
08/19/2024Pubmed ID
39158383Pubmed Central ID
PMC11391821DOI
10.1242/bio.060542Scopus ID
2-s2.0-85204886608 (requires institutional sign-in at Scopus site)Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder affecting 1:3500 male births and is associated with myofiber degeneration, regeneration, and inflammation. Glucocorticoid treatments have been the standard of care due to immunomodulatory/immunosuppressive properties but novel genetic approaches, including exon skipping and gene replacement therapy, are currently being developed. The identification of additional biomarkers to assess DMD-related inflammatory responses and the potential efficacy of these therapeutic approaches are thus of critical importance. The current study uses RNA sequencing of skeletal muscle from two mdx mouse models to identify high mobility group box 1 (HMGB1) as a candidate biomarker potentially contributing to DMD-related inflammation. HMGB1 protein content was increased in a human iPSC-derived skeletal myocyte model of DMD and microdystrophin treatment decreased HMGB1 back to control levels. In vivo, HMGB1 protein levels were increased in vehicle treated B10-mdx skeletal muscle compared to B10-WT and significantly decreased in B10-mdx animals treated with adeno-associated virus (AAV)-microdystrophin. However, HMGB1 protein levels were not increased in D2-mdx skeletal muscle compared to D2-WT, demonstrating a strain-specific difference in DMD-related immunopathology.
Author List
Slick RA, Sutton J, Haberman M, O'Brien BS, Tinklenberg JA, Mardikar A, Prom MJ, Beatka M, Gartz M, Vanden Avond MA, Siebers E, Mack DL, Gonzalez JP, Ebert AD, Nagaraju K, Lawlor MWAuthors
Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMelanie Gartz PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers
Disease Models, Animal
Dystrophin
HMGB1 Protein
Humans
Induced Pluripotent Stem Cells
Male
Mice
Mice, Inbred mdx
Muscle, Skeletal
Muscular Dystrophy, Duchenne
