This effect was also supported by immunohistochemistry where leiomyoma surgical specimens demonstrated decreased amount of FN1 and VCAN on UPA treatment.
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.
Myometrial cells in 3D culture responded to TGF-β3 with increased gene expression of collagen 1A1, fibronectin, and versican, and decreased expression of dermatopontin gene recapitulating the leiomyoma phenotype.
Immortalized leiomyoma and myometrial cells demonstrate increased mRNA and protein production of the ECM proteins, collagen 1A1 (15.0-fold), fibronectin 1 (2.93 fold), and connective tissue growth factor (9.40-fold) with exogenous TGF-beta3 stimulation.
To determine if curcumin has an antiproliferative effect on leiomyoma cells via apoptosis induction and whether curcumin impacts extracellular matrix (ECM) production by assessing the fibronectin expression in leiomyoma cells treated with curcumin.
Because GnRH and TGF-beta receptor signaling is in part mediated through the MAPK pathway, we determined whether the contribution of MAPK/ERK and transcriptional activation of c-fos and c-jun, result in differential regulation of type I collagen, fibronectin, and plasminogen activator inhibitor 1 (PAI-1) gene expression, whose products are known to influence extracellular matrix turnover, which is critical in leiomyoma growth and GnRHa-induced regression.
We characterized the localization of three ECM proteins, collagen type I, collagen type III, and fibronectin, in leiomyomas and adjacent normal myometrium.