Liarozole inhibits transforming growth factor β3 mediated extracellular matrix formation in human three dimensional leiomyoma cultures
Leiomyoma and myometrial cells in three-dimensional leiomyoma cultures treated with liarozole resulted in decreased expression of transforming growth factor b3 (TGF-b3) and TGF-b3-regulated extracellular matrix.
Gary Levy, M.D., Minnie Malik, Ph.D., Joy Britten, M.D., Melissa Gilden, B.S., James Segars, M.D., William H. Catherino, M.D., Ph.D.
Volume 102, Issue 1, Pages 272–281.e2
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.
Molecular and immunohistochemical analysis in a cell line evaluated in a three-dimensional culture.
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.
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.
Liarozole decreased TGF-β3 and TGF-β3–mediated extracellular matrix expression in a 3D uterine leiomyoma culture system.