Interacción entre el estradiol y la vía de señalización del NFkB en la expresión de leptina placentaria
Pregnancy success requires a proper fetal maternal interaction at the\nestablishment of implantation. Leptin has been described as a multitasking\ncytokine in reproduction and pregnancy, particularly in the placenta, where it acts\nas an autocrine hormone. The expression of leptin in normal trophobl...
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| Formato: | Tesis de maestría acceptedVersion |
| Lenguaje: | Español |
| Publicado: |
Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2022
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_7797 https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_7797.dir/7797.PDF |
| Aporte de: |
| Sumario: | Pregnancy success requires a proper fetal maternal interaction at the\nestablishment of implantation. Leptin has been described as a multitasking\ncytokine in reproduction and pregnancy, particularly in the placenta, where it acts\nas an autocrine hormone. The expression of leptin in normal trophoblastic cells is\nregulated by different endogenous signals, but the regulation of placental leptin\nexpression is still poorly understood. We have previously reported that 17?-\nestradiol up-regulates placental leptin expression through genomic and nongenomic\nmechanisms.\nTo improve the knowledge of estrogen receptor mechanisms in regulating leptin\ngene expression, we examined nuclear factor kappa B (NF?B) transcription factor\neffect on estradiol leptin induction in human BeWo cell line and human term\nplacental explants.\nWe demonstrated that estradiol induction effect on leptin expression is blocked by\nthe inhibition of NF?B signaling. We also found that the overexpression of p65\nsubunit, the active form of NF?B, induces leptin expression. Moreover, the\ndownregulation of estrogen receptor alpha (ER?) level through a specific siRNA,\nabolished NF?B effect on leptin expression. On the other hand we showed data that\ndemonstrate that ER? signaling increased NF?B signaling pathway activation in\ntrophoblastic cells. Estradiol treatment significantly increased p65 expression, and\nthe phosphorylation of the inhibitory protein ?B alpha (I?B?). A reporter plasmid\ncontaining NF?B elements was also induced in response to estradiol stimulation.\nAll these results suggest a crosstalk between ER? and NF?B. Supporting this idea,\nlocalization experiments revealed that estradiol treatment induced nuclear\nlocalization of overexpressed p65. Moreover, the overexpression of ER? produced\na complete displacement of both endogenous and overexpressed p65 protein to\nthe nuclear localization. Immunoprecipitation experiments showed the presence of\na complex containing ER? and NF?B.\nTaken together all these evidences suggest a cooperative behavior between\nER? and NF?B transcription factors to induce leptin transcription. |
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