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Growth differentiation factor 9 inhibits vascular endothelial growth factor expression in human granulosa cells. 2020

Congcong Guo, and Minghui Chen, and Wenmin Ma, and Bing Cai, and Yanwen Xu, and Yiping Zhong, and Canquan Zhou
Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

In aortic endothelial cells, the TGFβ signaling pathway is involved in the regulation of vascular endothelial growth factor (VEGF), which encodes a potent angiogenic factor crucial for the development of ovarian hyperstimulation syndrome. Growth differentiation factor 9 (GDF9) is a member of the TGFβ family and its effect on VEGF expression in human granulosa cells is unknown. In this study, human granulosa cells were collected from patients during the course of oocyte retrieval for in vitro fertilization and were cultured in vitro. After the first 48 h of culture, cells were treated with GDF9 with or without SB431542 (an ALK5 inhibitor) at various doses. The medium was then collected to determine the concentration of VEGF by ELISA. Cellular RNA was collected and extracted for quantification by real-time quantitative fluorescence PCR. Our study showed that GDF9 suppressed VEGF release from human granulosa cells in a dose-dependent manner and also downregulated VEGF mRNA levels in these cells. Furthermore, SB431542 antagonized the suppression of VEGF mRNA by GDF9 and diminished the inhibitory effect of GDF9 on VEGF release by human granulosa cells. Our results indicated that GDF9 can inhibit VEGF expression in human granulosa cells and ALK5 might mediate this process.

UI MeSH Term Description Entries
D004149 Dioxoles
D005260 Female Females
D006107 Granulosa Cells Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH). Cell, Granulosa,Cells, Granulosa,Granulosa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077293 Receptor, Transforming Growth Factor-beta Type I A transmembrane serine-threonine kinase that forms a heteromeric complex with TYPE II TGF-BETA RECEPTORS to bind TGF-BETA and regulate a variety of physiological and pathological processes including CELL CYCLE ARREST; CELL PROLIFERATION; CELL DIFFERENTIATION; WOUND HEALING; EXTRACELLULAR MATRIX production, immunosuppression and ONCOGENESIS. Activin Receptor-like Kinase 5,Receptor, TGF-beta Type I,Serine-Threonine-Protein Kinase Receptor R4,TGF-beta RPK,TGF-beta Receptor Protein Kinase,TGF-beta Type I Receptor,TGF-beta Type I Receptors,TGFBR1,TbetaR-I Kinase,Transforming Growth Factor beta Receptor I,Transforming Growth Factor, beta Receptor 1,Type I TGF-beta Receptor,Type I TGF-beta Receptors,Activin Receptor like Kinase 5,Kinase, TbetaR-I,Serine Threonine Protein Kinase Receptor R4,TGF beta Receptor Protein Kinase,TGF beta Type I Receptor,TGF beta Type I Receptors,TbetaR I Kinase,Type I TGF beta Receptor,Type I TGF beta Receptors
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001549 Benzamides BENZOIC ACID amides.
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D055429 Growth Differentiation Factor 9 A bone morphogenetic protein that plays an essential role in the regulation of ovarian folliculogenesis. GDF-9

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