| First Author | Urao N | Year | 2017 |
| Journal | Hum Mol Genet | Volume | 26 |
| Issue | 24 | Pages | 4951-4960 |
| PubMed ID | 29206970 | Mgi Jnum | J:252782 |
| Mgi Id | MGI:6095325 | Doi | 10.1093/hmg/ddx378 |
| Citation | Urao N, et al. (2017) Thrombospondin-1 and disease progression in dysferlinopathy. Hum Mol Genet 26(24):4951-4960 |
| abstractText | The purpose of this study was to determine whether thrombospondin (TSP)-1 promotes macrophage activity and disease progression in dysferlinopathy. First, we found that levels of TSP-1 are elevated in blood of non-ambulant dysferlinopathy patients compared with ambulant patients and healthy controls, supporting the idea that TSP-1 levels are correlated with disease progression. We then crossed dysferlinopathic BlaJ mice with TSP-1 knockout mice and assessed disease progression longitudinally with magnetic resonance imaging (MRI). In these mice, deletion of TSP-1 ameliorated loss in volume and mass of the moderately affected gluteal muscle but not of the severely affected psoas muscle. T2 MRI parameters revealed that loss of TSP-1 modestly inhibited inflammation only in gluteal muscle of male mice. Histological assessment indicated that deletion of TSP-1 reduced inflammatory cell infiltration of muscle fibers, but only early in disease progression. In addition, flow cytometry analysis revealed that, in males, TSP-1 knockout reduced macrophage infiltration and phagocytic activity, which is consistent with TSP-1-enhanced phagocytosis and pro-inflammatory cytokine induction in cultured macrophages. In summary, TSP-1 appears to play an accessory role in modulating Mp activity in BlaJ mice in a gender, age and muscle-dependent manner, but is unlikely a primary driver of disease progression of dysferlinopathy. |
