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

Objective: To investigate the effect of transforming growth factor (TGF)-beta 1 on the extracellular signal-regulated kinase (ERK) and Smad pathway and the role of peroxisome proliferator-activated receptor (PPAR)-gamma in cultured human endometrial stromal cells. Design: Experimental study. Setting: Infertility 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-beta 1, rosiglitazone (PPAR gamma 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 E-2 (PGE(2)) release., Result(S): TGF-beta 1 inhibited cellular proliferation and induced the expressions of COX-2, PGE(2), and PRL of cultured human endometrial stromal cells. These effects may be mediated by Smad, and ERK phosphorylation. Treatment with rosiglitazone, a PPAR gamma agonist, reversed the TGF-beta 1 effect by antagonizing the activation of ERK and Smad that was induced by TGF-beta 1. Conclusion(s): PPAR gamma plays a negative role by directly acting. on Smad and ERK phosphorylation in human endometrial cell decidualization that is induced by TGF-beta 1 in vitro.