Transforming growth factor (TGF)-beta1-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-beta1.

Abstract

OBJECTIVE: To investigate the effect of transforming growth factor (TGF)-beta1 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-beta1, rosiglitazone (PPARgamma 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-beta1 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 PPARgamma agonist, reversed the TGF-beta1 effect by antagonizing the activation of ERK and Smad that was induced by TGF-beta1.

CONCLUSION(S): PPARgamma plays a negative role by directly acting on Smad and ERK phosphorylation in human endometrial cell decidualization that is induced by TGF-beta1 in vitro.