Mifepristone inhibits extracellular matrix formation in uterine leiomyoma

Capsule:
Progestin stimulated extracellular matrix formation in immortalized human leiomyoma two-dimensional and three-dimensional cultures, and mifepristone inhibited progestin-stimulated extracellular matrix protein components involved in aberrant fibrosis.

Authors:
Amrita Patel, M.D., Minnie Malik, Ph.D., Joy Britten, M.D., Jeris Cox, M.D., William H. Catherino, M.D., Ph.D.

Volume 105, Issue 4, Pages 1102-

Abstract:

Objective:
To characterize the efficacy of mifepristone treatment on extracellular matrix (ECM) production in leiomyomas.

Design:
Laboratory study.

Setting:
University research laboratory.

Patient(s):
None.

Intervention(s):
Treatment of human immortalized two-dimensional (2D) and three-dimensional (3D) leiomyoma and myometrial cells with mifepristone and the progestin promegestone (R5020).

Main Outcome Measure(s):
Expression of COL1A1, fibronectin, versican variant V0, and dermatopontin in treated leiomyoma cells by Western blot analysis and confirmatory immunohistochemistry staining of treated 3D cultures.

Result(s):
Treatment with progestin stimulated production of COL1A1, fibronectin, versican, and dermatopontin. Mifepristone treatment inhibited protein production of these genes, most notably with versican expression. Combination treatment with both the agonist and antagonist further inhibited protein expression of these genes. Immunohistochemistry performed on 3D cultures demonstrated generalized inhibition of ECM protein concentration.

Conclusion(s):
Our study demonstrated that the progesterone agonist R5020 directly stimulated extracellular matrix components COL1A1, fibronectin, versican, and dermatopontin production in human leiomyoma cells. Progesterone antagonist mifepristone decreased protein production of these genes to levels comparable with untreated leiomyoma cells.

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