Turgeman, T., Institute of Animal Sciences, The Volcani Center, P.O. Box 6, Bet Dagan, 50250, Israel, Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Hagai, Y., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Huebner, K., Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Canada
Jassal, D.S., Institute of Cardiovascular Sciences, Cardiology Division, Department of Cardiac Sciences, Winnipeg, Man., Canada
Anderson, J.E., Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Canada
Genin, O., Institute of Animal Sciences, The Volcani Center, P.O. Box 6, Bet Dagan, 50250, Israel
Nagler, A., Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
Halevy, O., Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Pines, M., Institute of Animal Sciences, The Volcani Center, P.O. Box 6, Bet Dagan, 50250, Israel

Fibrosis is a known feature of dystrophic muscles, particularly the diaphragm, in the mdx mouse. In this study we evaluated the effect of halofuginone, a collagen synthesis inhibitor, on collagen synthesis in various muscles of young wild-type (C57/BL/6J) and mdx mice. Halofuginone prevented the age-dependent increase in collagen synthesis in the diaphragms of mdx with no effect on wild-type mice (n = 5 for each time point). This was associated with a decrease in the degenerated areas and number of central nuclei. Halofuginone also inhibited collagen synthesis in cardiac muscle. Moreover, enhanced motor coordination, balance and improved cardiac muscle function were observed implying reduced muscle injury. Halofuginone inhibited Smad3 phosphorylation downstream of TGFβ in the diaphragm and cardiac muscles, in C2 cell line and in primary mouse myoblast cultures representing various muscular dystrophies. We suggest that via its effect on Smad3 phosphorylation, halofuginone inhibits muscle fibrosis and improves cardiac and skeletal muscle functions in mdx mice. © 2008 Elsevier B.V. All rights reserved.