PLACENTAL LEPTIN EXPRESSION IS MEDIATED BY NFkB SIGNALING

MALENA SCHANTON; ANTONIO PÉREZ PÉREZ; YÉSICA GAMBINO; BERNARDO MASKIN; VÍCTOR SÁNCHEZ MARGALET; CECILIA L. VARONE

Simposio; VII SLIMP- Latin American Symposium on Maternal Fetal Interaction & Placenta; 2017

PLACENTAL LEPTIN EXPRESSION IS MEDIATED BY NFkB SIGNALINGM. Schanton1, A. Perez-P erez 2, Y. Gambino 1, B. Maskin 3, V. Sanchez- Margalet 2, C. Varone 1. 1Departamento de Química Biologica, FCEN, UBA, IQUIBICEN, CONICET, Buenos Aires, Argentina; 2Departamento deBioquímica Medica y Biología Molecular, Universidad de Sevilla, Seville,Spain; 3 Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, ArgentinaLeptin is a key hormone in placental physiology. Previous results demonstratedthat estradiol (E2) regulates leptin expression involving genomicand non-genomic effects.Objectives: Considering there is a potential binding site for NFkB between-2850 and -2838bp at the promoter sequence of leptin gene, and takinginto account the interaction between ERs and the NFkB factor, we analyzedthe involvement of this transcription factor in the effects of E2 on placentalleptin expression.Methods: BeWo cells were transiently transfected with the Rel A vectorwhich express the subunit p65, responsible for the activity of NFkB dimers.We performed experiments with placental explants and BeWo cellstreated with E2 for 48 hours in presence of sulfasalazine (an Ikk inhibitor),also BeWo-Sh2, were treated with doxycycline, western blot and qRT-PCRwere used to explore protein and transcript expression.Results: The expression of subunits p65 decreased significantly E2 effectson the transcriptional activity of pL1951 vector. We saw a markedly activityreduced of the basal leptin promoter. Similar results its seen with theBeWo-Sh2, which presents reduced level of Era protein. Suggesting thatthe overexpression of Rel A would inhibit the interaction of other factorswith their response element on the leptin promoter, for example ERsreceptors.Conclusion: The treatment with the drug reduces E2 action over theendogenous leptin expression, suggesting the participation of the NFkBdimers in the regulatory effect from this steroid. These provide new evidenceabout the mechanisms by which the E2 regulates the expression ofplacental leptin