Department of Neurology, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium.
Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Int J Mol Sci. 2022 Mar 17;23(6):3251. doi: 10.3390/ijms23063251.
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 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 mice aged 4, 8, 12, and 26 weeks. Necrosis was most prominent in 12 week-old 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 mice, but not in 26 week-old mice, whereas TauT levels in the diaphragm remained significantly lower in 26 week-old mice. In contrast, SMIT protein levels were significantly higher in the muscles of mice when compared to controls. Our study revealed differential regulation of osmolyte pathway members in 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.
杜氏肌营养不良症（DMD）是一种以肌肉进行性退化为特征的遗传疾病。渗透胁迫参与 DMD 病理学，已有报道称渗透调节物途径成员的水平发生改变。本研究的目的是通过检查渗透调节物途径成员的表达，包括牛磺酸转运体（TauT）、肌肌醇协同转运蛋白（SMIT）、甜菜碱 GABA 转运体（BGT）和醛糖还原酶（AR），来深入了解 4、8、12 和 26 周龄 小鼠模型中的渗透压变化。在 12 周龄的 小鼠中，坏死最为明显，而在前胫骨肌中，再生纤维的数量增加到 26 周。TauT 蛋白水平在前胫骨肌和比目鱼肌中从 4 到 12 周龄的 小鼠下调，但在 26 周龄的 小鼠中没有下调，而在 26 周龄的 小鼠中，膈肌中的 TauT 水平仍明显较低。相比之下，SMIT 蛋白水平在 小鼠的肌肉中明显高于对照组。我们的研究揭示了渗透调节物途径成员在 肌肉中的差异调节，这表明它们在 DMD 发病机制中的复杂参与超出了一般的渗透应激反应。这些结果突出了渗透调节物途径成员作为研究兴趣和未来在肌营养不良症中的治疗靶点的潜力。
