Myometrial cells undergo fibrotic transformation under the influence of transforming growth factor β-3

Objective: To examine the effect of transforming growth factor (TGF) β3 on immortalized myometrial and leiomyoma cell lines cloned from primary cell cultures of surgical specimens, and to determine whether such treatment alters myometrial cell extracellular matrix (ECM) expression. Design: Laboratory study. Setting: University hospital. Patient(s): Immortalized myometrial and leiomyoma cells from patients with symptomatic leiomyomata. Intervention(s): Tissue culture, followed by cellular, RNA, and protein analysis. Main Outcome Measure(s): Cell proliferation, alteration in ECM component expression. Result(s): 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-β3 stimulation. Notably, the expression of collagen 1A1, fibronectin 1, and connective tissue growth factor in myometrial cells increase to similar expression levels as those found in leiomyoma cells. In addition, TGF-β3 decreased production of genes involved in matrix resorption, including matrix metalloproteinase 2 (0.65-fold) and -11 (0.68-fold). Conclusion(s): TGF-β3 induced a molecular phenotype in myometrial cells that was similar to leiomyoma cells, with elevated production of ECM-related genes and decreased production of ECM degradation-related genes.