Biomaterial Database

WNT5A Enhances LH-Mediated Expression of HAS2 in Granulosa Cells. 2022

Qun Niu, and Jingjing Shi, and Qing Gao, and Jiang Fu

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

In adult ovary, WNT5A is involved in follicular responses to gonadotropins and necessary for ovarian follicle development. However, the mechanism by which gonadotropins regulate WNT5A and the role of WNT5A in modulating follicular responses to gonadotropins are unclear. In mice, we discovered that the expression of Wnt5a was increased in granulosa cells of mouse ovaries during ovulation, and regulated by gonadotropin-activated intra-ovarian cytokine interleukin 6 (IL6). Using human granulosa-like KGN cells, we confirmed that forskolin plus phorbol myristate acetate (PMA) which mimic the luteinizing hormone (LH) action induced the expression of WNT5A and cumulus expansion gene HAS2. However, this effect was suppressed by a NF-κB pathway inhibitor. Inhibition of NF-κB pathway also blocked the activation of WNT5A signaling components ROR2 and JNK. Moreover, exogenous WNT5A enhanced the expression of HAS2 in KGN cells through JNK and AKT signaling pathways. Knockdown of WNT5A expression by siRNA disrupted LH-mediated expression of HAS2. Our findings indicate that WNT5A could be a fine tuner for LH-induced HAS2 expression in ovarian granulosa cells.

UI	MeSH Term	Description	Entries
D007986	Luteinizing Hormone	A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.	ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
D010060	Ovulation	The discharge of an OVUM from a rupturing follicle in the OVARY.	Ovulations
D005260	Female		Females
D006062	Gonadotropins	Hormones that stimulate gonadal functions such as GAMETOGENESIS and sex steroid hormone production in the OVARY and the TESTIS. Major gonadotropins are glycoproteins produced primarily by the adenohypophysis (GONADOTROPINS, PITUITARY) and the placenta (CHORIONIC GONADOTROPIN). In some species, pituitary PROLACTIN and PLACENTAL LACTOGEN exert some luteotropic activities.	Gonadotropin
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
D000071818	Wnt-5a Protein	A Wnt protein and ligand for FRIZZLED RECEPTORS that may function as an inhibitor or activator of the WNT SIGNALING PATHWAY. For example, it activates signaling in the presence of Frizzled-4 but is inhibitory when coupled with ROR2 TYROSINE KINASE. It is required for axis formation during EMBRYOGENESIS and inhibits the proliferation, migration, and invasiveness of cancer cells.	Wingless-Type MMTV Integration Site Family, Member 5A,Wnt5a Protein,Wingless Type MMTV Integration Site Family, Member 5A,Wnt 5a Protein
D000076002	Hyaluronan Synthases	Membrane-associated glucuronosyltransferases that catalyze the reaction of UDP-N-acetyl-D-glucosamine and UDP-D-glucuronate to produce HYALURONAN. HYALURONAN SYNTHASE 2 (HAS2) is essential for embryogenesis and its expression by tumor cells is associated with metastasis.	HAS1 Protein,HAS2 Protein,HAS3 Protein,Hyaluronan Synthase,Hyaluronan Synthase 1,Hyaluronan Synthase 2,Hyaluronan Synthase 3,Hyaluronan Synthetase,Hyaluronate Synthase,Hyaluronate Synthetase,Hyaluronic Acid Synthetase,hasA Enzyme,3, Hyaluronan Synthase,Protein, HAS3,Synthase 1, Hyaluronan,Synthase 2, Hyaluronan,Synthase 3, Hyaluronan,Synthase, Hyaluronan,Synthase, Hyaluronate,Synthases, Hyaluronan,Synthetase, Hyaluronan,Synthetase, Hyaluronate,Synthetase, Hyaluronic Acid
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D016328	NF-kappa B	Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.	Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus