期刊
LIFE-BASEL
卷 11, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/life11111155
关键词
dystrophinopathy; aging; peripheral nervous system; rat; intestine; development
资金
- Duchenne Parent Project NL, Spieren voor spieren NL [SvS15]
- School for Mental Health and Neuroscience of Maastricht University
Dp71 protein is expressed highest in the distal intestine in neonatal and adult rats, with a regional difference observed at the protein level but not at the mRNA level. Dp co-localizes with aSMA and HuC/HuD in the muscularis propria, suggesting a potential role in GI comorbidities treatment.
Background: Gastrointestinal (GI) complaints are frequently noted in aging dystrophinopathy patients, yet their underlying molecular mechanisms are largely unknown. As dystrophin protein isoform 71 (Dp71) is particularly implicated in the development of smooth muscle cells, we evaluated its distribution in the neonatal and adult rat intestine in this study. Methods: Dp71 expression levels were assessed in the proximal (duodenum, jejunum and ileum) and distal (caecum, colon and rectum) intestine by Western blotting and qPCR. In addition, the cellular distribution of total Dp was evaluated in the duodenum and colon by immunohistochemical colocalization studies with alpha-smooth muscle actin (aSMA), Hu RNA binding proteins C and D (HuC/HuD) for neurons and vimentin (VIM) for interstitial cells. Results: In neonatal and adult rats, the distal intestine expressed 2.5 times more Dp71 protein than the proximal part (p < 0.01). This regional difference was not observed in Dp71 mRNA. During both stages, Dp-immunoreactivity was predominant in the muscularis propria, where it co-localized with aSMA and HuC/HuD. Conclusions: In neonatal and adult rats, Dp71 was expressed highest in the distal intestine. Together with the observation that Dp may be expressed by myenteric neurons, this warrants a paradigm shift in the treatment of GI comorbidities.
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