Liarozole inhibits transforming growth factor-β3-mediated extracellular matrix formation in human three-dimensional leiomyoma cultures

Gary Levy, Minnie Malik, Joy Britten, Melissa Gilden, James Segars, William H. Catherino

Research output: Contribution to journalArticle

Abstract

Objective To investigate the impact of liarozole on transforming growth factor-β3 (TGF-β3) expression, TGF-β3 controlled profibrotic cytokines, and extracellular matrix formation in a three-dimensional (3D) leiomyoma model system. Design Molecular and immunohistochemical analysis in a cell line evaluated in a three-dimensional culture. Setting Laboratory study. Patient(s) None. Intervention(s) Treatment of leiomyoma and myometrial cells with liarozole and TGF-β3 in a three-dimensional culture system. Main Outcome Measure(s) Quantitative real-time reverse-transcriptase polymerase chain reaction and Western blotting to assess fold gene and protein expression of TGF-β3 and TGF-β3 regulated fibrotic cytokines: collagen 1A1 (COL1A1), fibronectin, and versican before and after treatment with liarozole, and confirmatory immunohistochemical stains of treated three-dimensional cultures. Result(s) Both TGF-β3 gene and protein expression were elevated in leiomyoma cells compared with myometrium in two-dimensional and 3D cultures. Treatment with liarozole decreased TGF-β3 gene and protein expression. Extracellular matrix components versican, COL1A1, and fibronectin were also decreased by liarozole treatment in 3D cultures. Treatment of 3D cultures with TGF-β3 increased gene expression and protein production of COL1A1, fibronectin, and versican. Conclusion(s) Liarozole decreased TGF-β3 and TGF-β3-mediated extracellular matrix expression in a 3D uterine leiomyoma culture system.

Original languageEnglish (US)
Pages (from-to)272-281.e2
JournalFertility and sterility
Volume102
Issue number1
DOIs
StatePublished - Jul 2014
Externally publishedYes

Keywords

  • Extracellular matrix
  • leiomyoma
  • liarozole
  • three-dimensional model
  • transforming growth factor-beta

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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