Expression of the Pro-Fibrotic Marker Periostin in a Mouse Model of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is characterised by fibrotic tissue deposition in skeletal muscle. We assessed the role of periostin in fibrosis using 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 ( expression significantly exceeded that seen in wildtype controls at all timepoints analysed, with the highest expression at 5 months of age ( < 0.05). We found to be more consistently highly expressed at the earlier timepoints compared to established markers of fibrosis like transforming growth factor-beta 1 () and connective tissue growth factor (). Immunohistochemistry confirmed a significantly higher periostin protein expression in 5-month-old mice compared to age-matched healthy controls ( < 0.01), coinciding with a significant fibrotic area percentage ( < 0.0001). RT-qPCR also indicated an elevated expression of , (collagen type 1 alpha 1) and in DIAs compared to wild type controls ( < 0.05) at 8- and 12-month timepoints. Accordingly, immunoblot quantification demonstrated elevated periostin (3, 5 and 8 months, < 0.01) and Tgf-β1 (8 and 12 months, < 0.001) proteins in the 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.