NCBI Summary:
The Drosophila embryonic protein snail is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. [provided by RefSeq, Jul 2008]
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Comment
SNAIL mediates TGF-β1-induced down-regulation of pentraxin 3 expression in human granulosa cells. Li H et al. (2018) Transforming growth factor-β1 (TGF-β1) plays a critical role in regulating follicular development and its dysregulation has been shown to be involved in the pathogenesis of ovulation dysfunction. SNAIL is a well-known transcriptional repressor that mediates TGF-β1-induced cellular functions. Pentraxin 3 (PTX3) is a key enzyme for the assembly and stabilization of the cumulus oophorus extracellular matrix, which is essential for cumulus expansion during the periovulatory stage. The purpose of the present study was to investigate the roles of TGF-β1 and SNAIL in the regulation of PTX3 expression and to examine the underlying mechanism. An established immortalized human granulosa cell line (SVOG), a granulosa cell tumor cell line (KGN) and primary human granulosa-lutein cells were used as study models. We demonstrated for the first time that TGF-β1 treatment significantly decreased the mRNA and protein levels of PTX3. This suppressive effect was abolished by co-treatment with the soluble TβRII receptor or the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, SMAD2/3 or SMAD4 reversed the effects of TGF-β1-induced SNAIL up-regulation and PTX3 suppression. These results indicate that TGF-β1 up-regulates SNAIL and down-regulates PTX3 expression via a TβRII-ALK5-mediated SMAD-dependent signaling pathway in human granulosa cells. Additionally, TGF-β1-induced PTX3 suppression is mediated by up-regulation of the SNAIL transcription factor as knockdown of SNAIL completely reversed the suppression of PTX3 in response to TGF-β1. These findings may shed light on the roles of TGF-β1 and SNAIL in the regulation of follicular function and may provide therapeutic targets for the treatment of ovulation dysfunction.//////////////////TGF-β1 promotes hyaluronan synthesis by upregulating hyaluronan synthase 2 expression in human granulosa-lutein cells. Wang F et al. (2019) Hyaluronan serves as a structural component of ovarian follicles, and hyaluronan-mediated signaling cascades lead to follicular development, oocyte maturation, and ovulation. Transforming growth factor-β (TGF-β1) is highly expressed in human oocytes and granulosa cells and involved in the regulation of follicular development and ovulation. Previous studies have shown the imperative role for TGF-β signaling in the regulation of hyaluronan-mediated cumulus expansion and ovulation in human granulosa-lutein (hGL) cells. However, the detailed underlying molecular mechanisms by which TGF-β regulates the synthesis of hyaluronan in hGL cells are not fully elucidated. Using both primary and immortalized hGL cells as study models, we provide the first data showing that TGF-β1 significantly promoted the synthesis of hyaluronan by upregulating the expression of hyaluronan synthase 2 in these cells. Additionally, using dual inhibition approaches, we show that the TGF-β type II (TβRII) receptor and TGF-β type I (ALK5) receptor are functional receptors that mediate stimulatory effects in response to TGF-β1. Moreover, we found that the canonical SMAD2/SMAD3-SMAD4 signaling pathway is the principal intracellular signaling pathway that upregulates the expressionhyaluronan synthase and subsequent hyaluronan synthesis. Notably, we showed that SNAIL transcription factor is a critical molecule mediating the TGF-β signaling, which contributes to the increase in hyaluronan synthesis. These results of our in vitro studies suggest that intraovarian TGF-β1 plays a functional role in the local regulation of hyaluronan synthesis in hGL cells.//////////////////
Expression regulated by
Growth Factors/ cytokines
Comment
Bone morphogenetic protein 2 increases lysyl oxidase activity via up-regulation of snail in human granulosa-lutein cells. Bai L et al. (2018) Lysyl oxidase (LOX) is a copper-dependent enzyme that maintains and stabilizes the extracellular matrix (ECM) by catalyzing the cross-linking of elastin and collagen. ECM within the ovarian follicle plays a crucial role in regulating follicular development and oocyte maturation. Bone morphogenetic protein 2 (BMP2) belongs to the BMP subfamily that has been shown to be involved in the process of ovarian folliculogenesis and luteal formation. To date, whether BMP2 regulates the activity of LOX during human follicular development remains to be elucidated. The aim of this study was to investigate the effect of BMP2 on the regulation of LOX expression and activity in human granulosa-lutein cells (hGL) and the underlying mechanisms. Using both primary and immortalized (SVOG cells) hGL cells, we demonstrated that BMP2 up-regulated the expression and activity of LOX and hence decreased the soluble collagens in cultured medium in hGL cells. Additionally, the mRNA and protein levels of two transcriptional factors, SNAIL and SLUG, were increased following cell exposure to BMP2. Knockdown of SNAIL, but not SLUG partially reversed BMP2-induced increases in LOX expression and activity. The BMP2-induced up-regulation of SNAIL expression was abolished by the pre-treatment with two BMP type I receptor inhibitors, dorsomorphin and DMH-1, but not SB431542. Moreover, knockdown of SMAD4 completely abolished BMP2-induced up-regulation of SNAIL expression and the subsequent increases in LOX expression and activity. Our results suggest that BMP2 increases LOX expression and activity via the up-regulation of SNAIL in hGL cells. These findings may provide insights into the functional role of BMP2 in the regulation of ECM formation during folliculogenesis.//////////////////
Expression and localization of transcription factors SNAIL and SLUG in mouse ovaries and pre-implantation embryos. Guo C 2014 et al.
SNAIL and SLUG are zinc-finger transcription factors that participate in the regulation of cell division, cell survival, mesoderm formation and epithelial-to-mesenchymal transition. We investigate the expression of SNAIL and SLUG during follicular maturation, ovulation and luteinization in the ovaries of both neonatal mice and gonadotropin-induced immature mice. Furthermore, we examine the expression and localization of these transcription factors during early embryonic cleavage. Our data demonstrate that both SNAIL and SLUG are present in the epithelial cells of the ovarian surface in immature mice. SNAIL is first evident in the interstitial cells and theca cells by postnatal day (PD) 6 and then appears in the oocytes by PD 8, remaining at a constant expression level for all stages studied thereafter. SLUG is expressed in oocytes as early as PD 1. Its expression also increases with the development of the follicles in theca and interstitial cells but not in granulosa cells. In gonadotropin-induced immature mice, both SNAIL and SLUG are expressed in the corpora lutea. During early embryo cleavage, SNAIL occurs in the nucleus and cytoplasm of the majority of the embryo, excluding the nucleolus from the germinal vesicle breakdown (GVBD) to the 8-cell stage and is then localized in the cytoplasm during the morula stage and in the nucleus during the blastocyst stage. SLUG has an identical expression pattern as SNAIL from GVBD until the morula stage, except that it is localized in the cytoplasm during the blastocyst stage. Taken together, these different localization patterns suggest that SNAIL and SLUG probably play important roles during follicular development, luteinization and early embryonic development.
/////////////////////////