| Summary: | Duchenne muscular dystrophy (DMD) is characterised by fibrotic tissue deposition in skeletal muscle. We assessed the role of periostin in fibrosis using <i>mdx</i> mice, an established DMD murine model, for which we conducted a thorough examination of periostin expression over a year. RNA and protein levels in diaphragm (DIA) muscles were assessed and complemented by a detailed histological analysis at 5 months of age. In dystrophic DIAs, periostin (<i>Postn) mRNA</i> expression significantly exceeded that seen in wildtype controls at all timepoints analysed, with the highest expression at 5 months of age (<i>p</i> < 0.05). We found <i>Postn</i> to be more consistently highly expressed at the earlier timepoints compared to established markers of fibrosis like transforming growth factor-beta 1 (<i>Tgf-β1</i>) and connective tissue growth factor (<i>Ctgf</i>). Immunohistochemistry confirmed a significantly higher periostin protein expression in 5-month-old <i>mdx</i> mice compared to age-matched healthy controls (<i>p</i> < 0.01), coinciding with a significant fibrotic area percentage (<i>p</i> < 0.0001). RT-qPCR also indicated an elevated expression of <i>Tgf-β1</i>, <i>Col1α1</i> (collagen type 1 alpha 1) and <i>Ctgf</i> in <i>mdx</i> DIAs compared to wild type controls (<i>p</i> < 0.05) at 8- and 12-month timepoints. Accordingly, immunoblot quantification demonstrated elevated periostin (3, 5 and 8 months, <i>p</i> < 0.01) and Tgf-β1 (8 and 12 months, <i>p</i> < 0.001) proteins in the <i>mdx</i> muscle. These findings collectively suggest that periostin expression is a valuable marker of fibrosis in this relevant model of DMD. They also suggest periostin as a potential contributor to fibrosis development, with an early onset of expression, thereby offering the potential for timely therapeutic intervention and its use as a biomarker in muscular dystrophies.
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