Liu Pang-Pin, Chang Hsun-Ming, Cheng Jung-Chien, Leung Peter C K
Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Obstetrics and GynaecologyE-DA Hospital, Kaohsiung, Taiwan.
Reproduction. 2016 Dec;152(6):655-664. doi: 10.1530/REP-16-0262. Epub 2016 Sep 13.
Activin A is one of the members of transforming growth factor-β superfamily that is expressed in human large luteal cells, and may act in an autocrine/paracrine manner to regulate luteal function. Prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme and its derivative, prostaglandin E2 (PGE2), play significant roles in the regulation of corpus luteum formation and maintenance. To date, whether activin A can induce the expression of PTGS2 and the production of PGE2 in human granulosa-lutein cells is largely unknown. The aim of this study was to examine the effects of activin A on the regulation of PTGS2 expression and PGE2 production in human granulosa-lutein cells, and to investigate the underlying signal transduction mechanisms. In this study, the immortalized (SVOG cells) and primary human granulosa-lutein cells were used as the cell models. A TGF-β/activin type I receptor inhibitor, SB431542 and small interfering RNAs were used to investigate the activin A-induced downstream signaling pathway. We have demonstrated that activin A upregulated the expression of PTGS2 and increased the production of PGE2 via an ACVR1B-mediated SMAD2/3-SMAD4 signaling pathway. Our results suggest that activin A may be involved in the modulation of human corpus luteum formation via the induction of PTGS2 expression and PGE2 production.
激活素A是转化生长因子-β超家族的成员之一，在人黄体大细胞中表达，并可能以自分泌/旁分泌方式调节黄体功能。前列腺素内过氧化物合酶2（PTGS2）及其衍生物前列腺素E2（PGE2）在黄体形成和维持的调节中起重要作用。迄今为止，激活素A是否能诱导人颗粒黄体细胞中PTGS2的表达和PGE2的产生在很大程度上尚不清楚。本研究的目的是研究激活素A对人颗粒黄体细胞中PTGS2表达和PGE2产生的调节作用，并探讨其潜在的信号转导机制。在本研究中，永生化细胞（SVOG细胞）和原代人颗粒黄体细胞被用作细胞模型。使用一种转化生长因子-β/激活素I型受体抑制剂SB431542和小干扰RNA来研究激活素A诱导的下游信号通路。我们已经证明，激活素A通过ACVR1B介导的SMAD2/3-SMAD4信号通路上调PTGS2的表达并增加PGE2的产生。我们的结果表明，激活素A可能通过诱导PTGS2表达和PGE2产生参与人黄体形成的调节。
