Activin A-induced increase in LOX activity in human granulosa–lutein cells is mediated by CTGF

Chang, Hsun‐Ming; Cheng, Jung‐Chien; Liu, Yingtao; Klausen, Christian; Xu, Congjian

doi:10.1530/rep-16-0254

Cited by 27 publications

(15 citation statements)

References 52 publications

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“…The cells were pre-cultured to 50% confluence in antibiotic-free M199/MCDB105 medium containing 10% FBS and then transfected with 50 nM siRNA using Lipofectamine RNAiMAX (Life Technologies) for 24 h or 48 h, as previously described [38–41]. The knockdown efficiency for each target was confirmed using Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling

et al. 2017

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Epithelial ovarian carcinomas account for more than 90% of human ovarian cancers and have become the primary cause of death for gynecological malignancies. Unlimited cell proliferation and resistance to cell apoptosis contribute to the development of ovarian cancers. However, the underlying mechanisms involved in these processes in epithelial ovarian carcinomas are yet poorly understood. In the present study, we examined the Hippo signaling gene expression and investigated the effects of Sphingosine 1-phosphate (S1P) on cell proliferation and the underlying mechanisms in human ovarian cancer cell lines, OVCAR3 and SKOV3. Our results demonstrate that S1P disrupts Hippo signaling by reducing YAP phosphorylation and increasing the expression of CCN1 and CCN2 in both ovarian cancer cells. Furthermore, the increase in CCN1/CCN2 expression contributes to the S1P-induced increase in cancer cell proliferation.

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Section: Methodsmentioning

confidence: 99%

Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling

et al. 2017

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“…(2013a)GDF8ACVR2A, ACVR2BALK5SMAD2/3Chang et al . (2015d)Chang et al . (2016a, 2016b, 2016c)GDF9BMPR2ALK5SMAD2/3Mazerbourg and Hsueh (2006)Kaivo-Oja et al .…”

Section: Bmps and Bmp Receptorsmentioning

confidence: 99%

“…Primary hGL cells were used to generate the immortalized cells and the two display similar biological responses to many different treatments, such as LH, hCG, cAMP and various growth factors (Lie et al ., 1996). As demonstrated in numerous previous publications from our laboratory as well as those of other investigators, these cells are a widely accepted model to study the ovarian response during the periovulatory and early luteal phases (Havelock et al ., 2004; Chang et al ., 2015a, 2015c, 2016c, 2016a; Fang et al ., 2016a). COV434 and KGN are two widely used GC lines originating from ovarian GC tumors (van den Berg-Bakker et al ., 1993; Zhang et al ., 2000; Nishi et al ., 2001).…”

Section: Intra-ovarian Bmps and Oocyte–somatic Cell Interactionsmentioning

confidence: 99%

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

Chang

Qiao

Leung

2016

Hum. Reprod. Update

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BACKGROUNDInitially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation. This review summarizes the current knowledge on the physiological role and molecular determinants of these ovarian regulatory factors within the human germline-somatic regulatory loop.OBJECTIVE AND RATIONALEThe regulation of ovarian function remains poorly characterized in humans because, while the fundamental process of follicular development and oocyte maturation is highly similar across species, most information on the regulation of ovarian function is obtained from studies using rodent models. Thus, this review focuses on the studies that used human biological materials to gain knowledge about human ovarian biology and disorders and to develop strategies for preventing, diagnosing and treating these abnormalities.SEARCH METHODSRelevant English-language publications describing the roles of BMPs or growth differentiation factors (GDFs) in human ovarian biology and phenotypes were comprehensively searched using PubMed and the Google Scholar database. The publications included those published since the initial identification of BMPs in the mammalian ovary in 1999 through July 2016.OUTCOMESStudies using human biological materials have revealed the expression of BMPs, GDFs and their putative receptors as well as their molecular signaling in the fundamental cells (oocyte, cumulus/granulosa cells (GCs) and theca/stroma cells) of the ovarian follicles throughout follicle development. With the availability of recombinant human BMPs/GDFs and the development of immortalized human cell lines, functional studies have demonstrated the physiological role of intra-ovarian BMPs/GDFs in all aspects of ovarian functions, from follicle development to steroidogenesis, cell–cell communication, oocyte maturation, ovulation and luteal function. Furthermore, there is crosstalk between these potent ovarian regulators and the endocrine signaling system. Dysregulation or naturally occurring mutations within the BMP system may lead to several female reproductive diseases. The latest development of recombinant BMPs, synthetic BMP inhibitors, gene therapy and tools for BMP-ligand sequestration has made the BMP pathway a potential therapeutic target in certain human fertility disorders; however, further clinical trials are needed. Recent studies have indicated that GDF8 is an intra-ovarian factor that may play a novel role in regulating ovarian functions in the human ovary.WIDER IMPLICATIONSIntra-ovarian BMPs/GDFs are critical regulators of folliculogenesis and human ovarian functions. Any dysregulation or variations in these ligand...

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“…CCN2 is another critical intraovarian regulator; CCN2 cKO mice have disrupted follicular development, increased apoptosis of granulosa cells, decreased ovulation rates, and abnormal steroidogenesis in the ovary [9]. Our previous study showed that CCN2 plays a critical role in the regulation of extracellular matrix (ECM) formation and cell proliferation in human granulosa-lutein (hGL) cells [10,11,12]. Taken together, these results suggest that CCN1 and CCN2 are important intraovarian CCN proteins that modulate follicular development and ovulation.…”

Section: Introductionmentioning

confidence: 99%

CCN2 Mediates S1P-Induced Upregulation of COX2 Expression in Human Granulosa-Lutein Cells

Chang

et al. 2019

Cells

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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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Activin A-induced increase in LOX activity in human granulosa–lutein cells is mediated by CTGF

Cited by 27 publications

References 52 publications

Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling

Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

CCN2 Mediates S1P-Induced Upregulation of COX2 Expression in Human Granulosa-Lutein Cells

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