נגישות
menu      
חיפוש מתקדם
תחביר
חפש...
הספר "אוצר וולקני"
אודות
תנאי שימוש
ניהול
קהילה:
אסיף מאגר המחקר החקלאי
פותח על ידי קלירמאש פתרונות בע"מ -
Early pathological signs in young dysf−/− mice are improved by halofuginone
Year:
2020
Source of publication :
Neuromuscular Disorders
Authors :
גנין, אולגה
;
.
פינס, מרק
;
.
Volume :
30
Co-Authors:

Barzilai-Tutsch, H. - Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot, 76100, Israel.
Halevy, O. - Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot, 76100, Israel.

Facilitators :
From page:
472
To page:
482
(
Total pages:
11
)
Abstract:

Dysferlinopathies are a non-lethal group of late-onset muscular dystrophies. Here, we evaluated the fusion ability of primary myoblasts from young dysf−/− mice and the muscle histopathology prior to, and during early stages of disease onset. The ability of primary myoblasts of 5-week-old dysf−/− mice to form large myotubes was delayed compared to their wild-type counterparts, as evaluated by scanning electron microscopy. However, their fusion activity, as reflected by the presence of actin filaments connecting several cells, was enhanced by the antifibrotic drug halofuginone. Early dystrophic signs were already apparent in 4-week-old dysf−/− mice; their collagen level was double that in wild-type mice and continued to rise until 5 months of age. Continuous treatment with halofuginone from 4 weeks to 5 months of age reduced muscle fibrosis in a phosphorylated-Smad3 inhibition-related manner. Halofuginone also enhanced myofiber hypertrophy, reduced the percentage of centrally nucleated myofibers, and increased muscle performance. Together, the data suggest an inhibitory effect of halofuginone on the muscle histopathology at very early stages of dysferlinopathy, and enhancement of muscle performance. These results offer new opportunities for early pharmaceutical treatment in dysferlinopathies with favorable outcomes at later stages of life.

Note:
Related Files :
Differentiation
dysferlinopathy
Fibrosis
Fusion
Halofuginone
hypertrophy
עוד תגיות
תוכן קשור
More details
DOI :
10.1016/j.nmd.2020.04.001
Article number:
0
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
48006
Last updated date:
02/03/2022 17:27
Creation date:
01/06/2020 15:16
You may also be interested in
Scientific Publication
Early pathological signs in young dysf−/− mice are improved by halofuginone
30

Barzilai-Tutsch, H. - Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot, 76100, Israel.
Halevy, O. - Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot, 76100, Israel.

Early pathological signs in young dysf−/− mice are improved by halofuginone

Dysferlinopathies are a non-lethal group of late-onset muscular dystrophies. Here, we evaluated the fusion ability of primary myoblasts from young dysf−/− mice and the muscle histopathology prior to, and during early stages of disease onset. The ability of primary myoblasts of 5-week-old dysf−/− mice to form large myotubes was delayed compared to their wild-type counterparts, as evaluated by scanning electron microscopy. However, their fusion activity, as reflected by the presence of actin filaments connecting several cells, was enhanced by the antifibrotic drug halofuginone. Early dystrophic signs were already apparent in 4-week-old dysf−/− mice; their collagen level was double that in wild-type mice and continued to rise until 5 months of age. Continuous treatment with halofuginone from 4 weeks to 5 months of age reduced muscle fibrosis in a phosphorylated-Smad3 inhibition-related manner. Halofuginone also enhanced myofiber hypertrophy, reduced the percentage of centrally nucleated myofibers, and increased muscle performance. Together, the data suggest an inhibitory effect of halofuginone on the muscle histopathology at very early stages of dysferlinopathy, and enhancement of muscle performance. These results offer new opportunities for early pharmaceutical treatment in dysferlinopathies with favorable outcomes at later stages of life.

Scientific Publication
You may also be interested in