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Zinc finger gene 217 (ZNF217) Promoted Ovarian Hyperstimulation Syndrome (OHSS) through Regulating E2 Synthesis and Inhibiting Thrombospondin-1 (TSP-1). Zhai J et al. (2017) Zinc finger gene 217 (ZNF217) is a candidate gene of polycystic ovary syndrome (PCOS) which is vulnerable to ovarian hyperstimulation syndrome (OHSS). However, the relationship between ZNF217 and OHSS is largely unknown. Our study demonstrated that ZNF217 was mainly distributed in the granulosa cells of rat ovary. Significantly higher expression of ovarian ZNF217 was detected in OHSS rats, being consistent with serum 17β-estradiol concentration and ovarian aromatase. Moreover, OHSS rats also showed decreased ovarian TSP-1 mRNA, an acknowledged VEGF signaling suppressor. The same changes were detected in human granulosa cells and follicular fluid. Thus, the increased ZNF217 and decreased TSP-1 may participate in OHSS onset. In vitro experiment revealed that ZNF217 positively regulated E2 synthesis through promoting cAMP response element binding protein (CREB) and thereby CYP19A1 in KGN cells. Furthermore, ZNF217 negatively regulated TSP-1 in KGN cells while TSP-1 promoted claudin1 and inhibited nitric oxide (NO) in HUVECs and HAECs. Both of claudin1 and NO are responsible for the regulation of vascular permeability (VP). Therefore, we demonstrated that ZNF217 contributed to OHSS onset through promoting E2 synthesis and the increase of VP. Moreover, the increased ZNF217 and decreased TSP-1 provided new targets for the prevention or treatment of OHSS in the future.//////////////////
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Comment |
Rangel LB, et al reported that tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in
ovarian cancer but not in ovarian cystadenomas.
Because
claudin-3 and claudin-4 have been proposed to be expressed in epithelial ovarian cancer, we have
performed a detailed analysis of CLDN3 and CLDN4 expression in a panel of ovarian tumors of
various subtypes and cell lines. We also investigated whether high expression of claudin-3 and
claudin-4 was associated with TJ function in ovarian cancer cells. RNA was
obtained from a panel of 39 microdissected epithelial ovarian tumors of various histological
subtypes for real-time reverse transcription-PCR analysis. In addition, a total of 70 cases of ovarian
carcinomas, ovarian cysts, and normal ovarian epithelium from a tissue array were analyzed by
immunohistochemistry. Finally, a panel of cell lines was used for Western analysis of claudin
expression and TJ permeability studies. RESULTS: Although expressed at low levels in some
normal human tissues, including the ovary, CLDN3 and CLDN4 are highly up-regulated in epithelial
ovarian cancers of all subtypes. Immunohistochemical analyses using our ovarian tissue array
confirmed the high level of expression of claudin-3 and claudin-4 in the majority of ovarian
carcinomas, including many tumors exhibiting cytoplasmic staining. Ovarian cystadenoma did not
frequently overexpress these proteins, suggesting that the expression of these proteins is associated
with malignancy. In ovarian cancer cell lines, claudin-3 and claudin-4 expression was not
associated with functional TJs as measured by transepithelial electrical resistance.
CONCLUSIONS: These results show that CLDN3 and CLDN4 are frequently up-regulated in
ovarian tumors and cell lines and may represent novel markers for this disease. Overexpression of
these genes in ovarian cancer also suggests interesting scenarios for the involvement of TJ in
tumorigenesis. A better knowledge of the mechanisms underlying ovarian tumorigenesis will likely
result in the development of novel approaches for the diagnosis and therapy of this deadly disease.
Expression of claudins 1, 4, 5, and 7 in ovarian tumors of diverse types. Soini Y et al. SUMMARY:: In this study, 60 different types of ovarian lesions, mainly consisting of ovarian neoplasms, were studied for the expression of claudins 1, 4, 5, and 7. Strong expression of claudins 1, 4, and 7 was seen in benign and malignant epithelial ovarian tumors. Expression of claudin 5, reported to be mainly present in endothelial cells, was seen in ovarian epithelial tumors, but with a significantly lower frequency than claudins 1, 4, and 7. On the contrary, sex-cord stromal tumors and cysts, such as fibromas/thecomas, Sertoli-Leydig cell tumors, granulosa cell tumors, and follicular and luteinized cysts were mainly negative for claudins 1, 4, 5, and 7. Interestingly, adenomatoid tumors did not express claudin 5, which is in agreement with their non-endothelial nature. They were also negative for claudin 4, but expressed claudins 1 and 7, but to a lesser degree than epithelial lesions. In immature teratomas, the epithelial component was usually positive whereas other components were negative for these claudins. Dysgerminomas did not express any of the claudins studied. The results show that claudins 1, 4, and 7 are mainly expressed in ovarian epithelial tumors and can thus be used to indicate epithelial differentiation in them. Eventhough considered an endothelial marker, claudin 5 was also present in a subset of epithelial lesions. However, this claudin can be used to differentiate adenomatoid tumors from vascular lesions. No significant difference was seen between epithelial benign and malignant lesions, except for claudin 5, which seemed stronger in malignant epithelial tumors.
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