Tranilast, an orally active antiallergic compound, inhibits extracellular matrix production in human uterine leiomyoma and myometrial cells

Abstract

To determine the effect of tranilast (an antiallergic drug known to suppress fibrosis or to stabilize mast cells) on extracellular matrix production in human leiomyoma and myometrial cells. Laboratory study. University-affiliated laboratory. Seven premenopausal women who were admitted to the hospital for myomectomy or hysterectomy. Cells were treated with tranilast (300μM) for 48hours to measure extracellular matrix and activin-A expression by real-time reverse-transcription polymerase chain reaction and/or immunocytochemistry. The expression of fibronectin, collagen1A1, versican, and activin-A in myometrial and leiomyoma cells. Tranilast decreased fibronectin, collagen 1A1, and versican messenger RNA (mRNA) expression in human primary leiomyoma cell culture. Similar results were found in an immortalized human leiomyoma cell line. Tranilast also decreased the mRNA expression of fibronectin, collagen 1A1, and versican in human primary myometrial cells. The reduced expression of fibronectin and collagen 1 were observed by immunocytochemistry as well. Tranilast also reduced profibrotic growth factor, activin-A mRNA expression in primary myometrial and leiomyoma cells. Our results indicate that tranilast reduced fibronectin, collagen 1A1, versican, and activin-A expression in leiomyoma and myometrial cells, demonstrating its potential as an antifibrotic therapy for human leiomyomas.