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Promethazine Hydrochloride Inhibits Ectopic Fat Cell Formation in Skeletal Muscle.
- Source :
-
The American journal of pathology [Am J Pathol] 2017 Dec; Vol. 187 (12), pp. 2627-2634. Date of Electronic Publication: 2017 Sep 15. - Publication Year :
- 2017
-
Abstract
- Fatty degeneration of skeletal muscle leads to muscle weakness and loss of function. Preventing fatty degeneration in skeletal muscle is important, but no drug has been used clinically. In this study, we performed drug repositioning using human platelet-derived growth factor receptor α (PDGFRα)-positive mesenchymal progenitors that have been proved to be an origin of ectopic adipocytes in skeletal muscle. We found that promethazine hydrochloride (PH) inhibits adipogenesis in a dose-dependent manner without cell toxicity. PH inhibited expression of adipogenic markers and also suppressed phosphorylation of cAMP response-element binding protein, which was reported to be a primary regulator of adipogenesis. We established a mouse model of tendon rupture with intramuscular fat deposition and confirmed that emerged ectopic adipocytes are derived from PDGFRα <superscript>+</superscript> cells using lineage tracing mice. When these injured mice were treated with PH, formation of ectopic adipocytes was suppressed significantly. Our results show that PH inhibits PDGFRα <superscript>+</superscript> mesenchymal progenitor-dependent ectopic adipogenesis in skeletal muscle and suggest that treatment with PH can be a promising approach to prevent fatty degeneration of skeletal muscle.<br /> (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adipocytes pathology
Adipogenesis drug effects
Animals
Drug Repositioning
Humans
Mesenchymal Stem Cells drug effects
Mice
Mice, Inbred C57BL
Platelet-Derived Growth Factor metabolism
Adipocytes drug effects
Cell Differentiation drug effects
Histamine H1 Antagonists pharmacology
Muscle, Skeletal pathology
Promethazine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 187
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 28919111
- Full Text :
- https://doi.org/10.1016/j.ajpath.2017.08.008