Transforming growth factor (TGF)-β1-induced human endometrial stromal cell decidualization through extracellular signal-regulated kinase and Smad activation in vitro: peroxisome proliferator-activated receptor gamma acts as a negative regulator of TGF-β1

ObjectiveTo investigate the effect of transforming growth factor (TGF)-β1 on the extracellular signal-regulated kinase (ERK) and Smad pathway and the role of peroxisome proliferator-activated receptor (PPAR)-γ in cultured human endometrial stromal cells.DesignExperimental study.SettingInfertility center of a tertiary university hospital.Material(s)Human endometrial tissues obtained by hysterectomy from patients with conditions other than endometrial diseases.Intervention(s)Endometrial stromal cells were cultured under normal laboratory conditions. TGF-β1, rosiglitazone (PPARγ agonist), and PD98059 (ERK inhibitor) were added to endometrial stromal cell culture according to experimental purposes.Main Outcome Measure(s)Cell count, PRL expression, Smad and ERK phosphorylation, cyclooxygenase (COX)-2 expression, and prostaglandin E2 (PGE2) release.Result(s)TGF-β1 inhibited cellular proliferation and induced the expressions of COX-2, PGE2, and PRL of cultured human endometrial stromal cells. These effects may be mediated by Smad and ERK phosphorylation. Treatment with rosiglitazone, a PPARγ agonist, reversed the TGF-β1 effect by antagonizing the activation of ERK and Smad that was induced by TGF-β1.Conclusion(s)PPARγ plays a negative role by directly acting on Smad and ERK phosphorylation in human endometrial cell decidualization that is induced by TGF-β1 in vitro.