Promethazine Hydrochloride Inhibits Ectopic Fat Cell Formation in Skeletal Muscle

Takehiro Kasai, Masashi Nakatani, Naoki Ishiguro, Kinji Ohno, Naoki Yamamoto, Mitsuhiro Morita, Harumoto Yamada, Kunihiro Tsuchida, Akiyoshi Uezumi

Research output: Contribution to journalArticle

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+ 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+ 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.

Original languageEnglish
Pages (from-to)2627-2634
Number of pages8
JournalAmerican Journal of Pathology
Volume187
Issue number12
DOIs
Publication statusPublished - 01-12-2017

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Promethazine
Adipocytes
Skeletal Muscle
Platelet-Derived Growth Factor Receptors
Adipogenesis
Drug Repositioning
Cyclic AMP Response Element-Binding Protein
Muscle Weakness
Cell Lineage
Tendons
Rupture
Fats
Phosphorylation
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Kasai, Takehiro ; Nakatani, Masashi ; Ishiguro, Naoki ; Ohno, Kinji ; Yamamoto, Naoki ; Morita, Mitsuhiro ; Yamada, Harumoto ; Tsuchida, Kunihiro ; Uezumi, Akiyoshi. / Promethazine Hydrochloride Inhibits Ectopic Fat Cell Formation in Skeletal Muscle. In: American Journal of Pathology. 2017 ; Vol. 187, No. 12. pp. 2627-2634.
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Promethazine Hydrochloride Inhibits Ectopic Fat Cell Formation in Skeletal Muscle. / Kasai, Takehiro; Nakatani, Masashi; Ishiguro, Naoki; Ohno, Kinji; Yamamoto, Naoki; Morita, Mitsuhiro; Yamada, Harumoto; Tsuchida, Kunihiro; Uezumi, Akiyoshi.

In: American Journal of Pathology, Vol. 187, No. 12, 01.12.2017, p. 2627-2634.

Research output: Contribution to journalArticle

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