| First Author | Urao N | Year | 2016 |
| Journal | Neuromuscul Disord | Volume | 26 |
| Issue | 3 | Pages | 240-51 |
| PubMed ID | 26927626 | Mgi Jnum | J:345732 |
| Mgi Id | MGI:6838653 | Doi | 10.1016/j.nmd.2016.01.002 |
| Citation | Urao N, et al. (2016) Thrombospondin-1 levels correlate with macrophage activity and disease progression in dysferlin deficient mice. Neuromuscul Disord 26(3):240-51 |
| abstractText | Dysferlinopathy is associated with accumulation of thrombospondin (TSP)-1 and macrophages, both of which may contribute to the pathogenesis of the disease. The purpose of this study was to determine whether TSP-1 levels can predict macrophage activity and disease progression in dysferlin deficient BlaJ mice, focusing on the early disease process. In 3 month-old BlaJ mice, muscle TSP-1 levels exhibited strong positive correlations with both accumulation of F4/80hi macrophages and with their in vivo phagocytic activity in psoas muscles as measured by magnetic resonance imaging and flow cytometry. Muscle TSP-1 levels also exhibited a strong negative correlation with muscle mass and strong positive correlations with histological measurements of muscle fiber infiltration and regeneration. Over the course of disease progression from 3 to 12 months of age, muscle TSP-1 levels showed more complicated relationships with macrophage activity and an inverse relationship with muscle mass. Importantly, blood TSP-1 levels showed strong correlations with macrophage activity and muscle degeneration, particularly early in disease progression in BlaJ mice. These data indicate that TSP-1 may contribute to a destructive macrophage response in dysferlinopathy and pose the intriguing possibility that TSP-1 levels may serve as a biomarker for disease progression. |
