Effect of Transforming Growth Factor (TGF)-beta and Peroxisome Proliferator-Activated Receptor (PPAR)-gamma in Endometrial Decidualization. |
Jong Hee Kwon, Jae Hoon Lee, Hye Jin Chang, Dong Wook Park, Young Ah Kim, Mi Ran Kim, Kyung Joo Hwang |
1Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea. kjhwang74@hanmail.net 2Department of Biological Sciences, Ajou University, Suwon, Korea. 3Department of Obstetrics and Gynecology, Ilsan Paik Hospital, Inje University, Ilsan, Korea. |
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Abstract |
OBJECTIVE To ascertain the expression of transforming growth factor (TGF)-beta receptors in normal human endometrium during the menstrual cycle, and the action of TGF-beta and peroxisome proliferator-activated receptor (PPAR)-gamma during endometrial decidualization using cultured human endometrial stromal cells. METHODS: Human endometrial tissues were examined immunohistochemically for the expression of TGF-beta receptors and Smad. Western blotting, confocal microscopy and viable cell counting were performed on cultured human endometrial stromal cells which were treated with TGF-beta (10 ng/mL) and PPAR-gamma agonists (Rosiglitazone(R) 50 nM). Thereafter we compared the effect of TGF-beta and PPAR-gamma on the Smad phosphorylation, prolactin expression, and cellular proliferation in vitro human endometrial decidualization. RESULTS: The results revealed significantly increased expression of both TGF-beta receptor-I and -II proteins in the secretory stromal cells compared to the epithelial cells of human endometrium. The degree of expression and translocation into the nucleus of the phosphorylated Smad2/3 was also increased in the secretory endometrium compared to the proliferative endometrium. In the stromal cell culture, the decidualization process associated with TGF-beta and pSmad is inhibited by the PPAR-gamma agonist. In contrast to the PPAR-gamma agonist, TGF-beta inhibits cellular proliferation. CONCLUSION: TGF-beta/Smad signaling pathway is essential for endometrial decidualization and closely related to cellular differentiation. PPAR-gamma plays a conflicting role by directly acting on the Smad protein and blocking the TGF-beta/Smad signaling pathway. |
Key Words:
Endometrial stromal cell, Decidualization, TGF-beta, Smad, PPAR-gamma |
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