Description of Osmolyte Pathways in Maturing <i>Mdx</i> Mice Reveals Altered Levels of Taurine and Sodium/Myo-Inositol Co-Transporters
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration. Osmotic stress participates to DMD pathology and altered levels of osmolyte pathway members have been reported. The goal of this study was to gain insight in osmoregulatory changes in the <i&...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/6/3251 |
| Summary: | Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration. Osmotic stress participates to DMD pathology and altered levels of osmolyte pathway members have been reported. The goal of this study was to gain insight in osmoregulatory changes in the <i>mdx</i> mouse model by examining the expression of osmolyte pathway members, including taurine transporter (TauT), sodium myo-inositol co-transporter (SMIT), betaine GABA transporter (BGT), and aldose reductase (AR) in the skeletal muscles and diaphragm of <i>mdx</i> mice aged 4, 8, 12, and 26 weeks. Necrosis was most prominent in 12 week-old <i>mdx</i> mice, whereas the amount of regenerated fibers increased until week 26 in the tibialis anterior. TauT protein levels were downregulated in the tibialis anterior and gastrocnemius of 4 to 12 week-old <i>mdx</i> mice, but not in 26 week-old mice, whereas TauT levels in the diaphragm remained significantly lower in 26 week-old <i>mdx</i> mice. In contrast, SMIT protein levels were significantly higher in the muscles of <i>mdx</i> mice when compared to controls. Our study revealed differential regulation of osmolyte pathway members in <i>mdx</i> muscle, which points to their complex involvement in DMD pathogenesis going beyond general osmotic stress responses. These results highlight the potential of osmolyte pathway members as a research interest and future therapeutic target in dystrophinopathy. |
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| ISSN: | 1661-6596 1422-0067 |