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CCN2 Mediates S1P-Induced Upregulation of COX2 Expression in Human Granulosa-Lutein Cells.
Hu, Liao-Liao; Chang, Hsun-Ming; Yi, Yuyin; Liu, Yingtao; Taylor, Elizabeth L; Zheng, Li-Ping; Leung, Peter C K.
Afiliación
  • Hu LL; Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China.
  • Chang HM; Jiangxi Key Laboratory of Reproductive Physiology and Pathology, Nanchang University, Nanchang, Jiangxi 330031, China.
  • Yi Y; Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V6H3V5, Canada.
  • Liu Y; Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V6H3V5, Canada.
  • Taylor EL; Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V6H3V5, Canada.
  • Zheng LP; Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V6H3V5, Canada.
  • Leung PCK; Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V6H3V5, Canada.
Cells ; 8(11)2019 11 15.
Article en En | MEDLINE | ID: mdl-31731760
CCN1 and CCN2 are members of the CCN family and play essential roles in the regulation of multiple female reproductive functions, including ovulation. Cyclooxygenase-2 (COX2) is a critical mediator of ovulation and can be induced by sphingosine-1-phosphate (S1P) through the S1P1/3-mediated Yes-associated protein (YAP) signaling. However, it is unclear whether CCN1 or CCN2 can mediate S1P-induced upregulation of COX2 expression and increase in prostaglandin E2 (PGE2) production in human granulosa-lutein (hGL) cells. In the present study, we investigated the effects of S1P on the expressions of CCN1 and CCN2 in hGL cells. Additionally, we used a dual inhibition approach (siRNA-mediated silencing and small molecular inhibitors) to investigate the molecular mechanisms of S1P effects. Our results showed that S1P treatment significantly upregulated the expression of CCN1 and CCN2 in a concentration-dependent manner in hGL cells. Additionally, inhibition or silencing of S1P1, but not S1P3, completely abolished the S1P-induced upregulation of CCN2 expression. Furthermore, we demonstrated that S1P-induced nuclear translocation of YAP and inhibition or silencing of YAP completely abolished the S1P-induced upregulation of CCN1 and CCN2 expression. Notably, silencing of CCN2, but not CCN1, completely reversed the S1P-induced upregulation of COX2 expression and the increase in PGE2 production. Thus, CCN2 mediates the S1P-induced upregulation of COX2 expression through the S1P1-mediated signaling pathway in hGL cells. Our findings expand our understanding of the molecular mechanism underlying the S1P-mediated cellular activities in the human ovary.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingosina / Factores de Transcripción / Lisofosfolípidos / Proteínas de Ciclo Celular / Ciclooxigenasa 2 / Factor de Crecimiento del Tejido Conjuntivo / Proteína 61 Rica en Cisteína / Células Lúteas Límite: Female / Humans Idioma: En Revista: Cells Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingosina / Factores de Transcripción / Lisofosfolípidos / Proteínas de Ciclo Celular / Ciclooxigenasa 2 / Factor de Crecimiento del Tejido Conjuntivo / Proteína 61 Rica en Cisteína / Células Lúteas Límite: Female / Humans Idioma: En Revista: Cells Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza