In this study, we explored the role of
estrogen-mediated activation of stromal fibroblasts in the pathogenesis of
uterine fibroid in patients. We isolated
uterine fibroids and surrounding smooth muscle from patients and separated fibroblasts using immunomagnetic beads. We also measured the expression levels of
estrogen receptors in fibroblasts and examined cell proliferation, expressions of fibroblast activation
protein (FAP), extracellular matrix (ECM) (
fibronectin,
laminin,
collagen I),
growth factors (transforming growth factor-β,
insulin-like growth factor-1), and cell proliferation pathway stimulated by
estrogen. We also silenced the expression of FAP by RNA interference and analyzed the expression levels of these markers before and after E2 stimulation. Finally, we also investigated the effect of activated fibroblast supernatant on cell proliferation of fibroblasts, smooth muscle cells, and
fibroid cells. We found that fibroblasts in
uterine fibroid were activated, and the expression levels of
estrogen receptors from
fibroid cells were higher than those from smooth muscle cells. After
estrogen stimulation, the proliferation activity of fibroblast was enhanced, and the expression of FAP, ECM, and
growth factors was increased; the signaling pathway involved in cell proliferation was also activated. Interestingly, the activated fibroblast supernatant stimulation can promote cell proliferation. Silencing of FAP expression could inhibit the E2-mediated
biological effects. In conclusion,
estrogen promotes proliferation of
uterine fibroids through the activation of fibroblasts, thus, activated fibroblasts may play an important role in the pathogenesis of
uterine fibroids, which could be targeted in future for the treatment of
uterine fibroid.