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

Capsule:
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.

Authors:
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

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.

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