Publication:
Hydroxy group requirement for halofuginone-dependent inhibition of muscle fibrosis and improvement of histopathology in the mdx mouse model for Duchenne muscular dystrophy

Simple item page
dc.contributor.authorWellner, Gili
dc.contributor.authorMordechay, Sharon
dc.contributor.authorEvans, Paul
dc.contributor.authorGenin, Olga
dc.contributor.authorPines, Mark
dc.contributor.authorHalevy, Orna
dc.date.accessioned2022-07-05T08:07:08Z
dc.date.available2022-07-05T08:07:08Z
dc.date.issued2019
dc.description.abstractIn Duchenne muscular dystrophy (DMD), the progressive loss of muscle and its ability to function is associated with significant fibrosis, representing the major disease complication in patients. Halofuginone, a halogenated analog of the naturally occurring febrifugine, has been shown to prevent fibrosis in various animal models, including those of muscular dystrophies. Here, two optically active enantiomers of deoxyhalofuginone—a halofuginone analogue in which the hydroxy group in position 3 was removed from the piperidinyl entity—were evaluated with respect to their effect on muscle histopathology in mdx mice. Male mdx mice were treated with either deoxyhalofuginone (as single enantiomers or in racemic form), or halofuginone, for 10 weeks, starting at the age of 4 weeks. Halofuginone caused a significant reduction in total collagen content, degenerative areas, as well as in utrophin and phosphorylated-Smad3 levels in the mdx diaphragms. However, neither the deoxyhalofuginone enantiomers, nor its racemic form had any effect on these parameters. A positive effect of the deoxyhalofuginone (+)-enantiomer was observed on myofiber diameters; however, it was lesser than that of halofuginone. It is concluded that the hydroxy group plays a key role in halofuginone’s effects related to fibrosis in DMD, and points towards the transforming growth factor β/Smad3 signaling pathway being involved in this inhibition. Elucidation of the structure–function relationship of halofuginone, in relation to inhibiting fibrosis in muscular dystrophies, is of the utmost importance for creating the next generation of anti-fibrotic therapies that will be more efficacious and less toxic, hence improving life quality of patients.es
dc.formatapplication/pdfes
dc.format.extent11es
dc.identifier.doiDOI: 10.14670/HH-18-083
dc.identifier.eisbnHistology and Histopathology, Vol.34, nº7, (2019)es
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/122129
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectSkeletal musclees
dc.subjectDuchenne muscular dystrophyes
dc.subjectFibrosises
dc.subjectUtrophines
dc.subjectHalofuginonees
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleHydroxy group requirement for halofuginone-dependent inhibition of muscle fibrosis and improvement of histopathology in the mdx mouse model for Duchenne muscular dystrophyes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Wellner-34-791-801-2019.pdf
Size:
21.01 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.39 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Histology and histopathology Vol.34, nº7 (2019)