VIP induces human trophoblast cell migration and invasion through VPAC2 receptors and autocrine circuits involving camp/pka/cre signaling

D. VOTA, V. HAUK, A. TORO, D. PAPARINI, F. MERECH, C.VARONE, R. RAMHORST ADN C. PÉREZ LEIRÓS.

Cappadocia

Simposio; 12th Internatinal Symposium of VIP, VPAC and related pepetides; 2015

12th Internatinal Symposium of VIP, VPAC and related pepetides

The generation of the human maternal-placental interface involves the differentiation of trophoblast cells to phenotypes suitable for migration and invasion of the deciduas. We have recently proposed that VIP contributes to immune homeostasis maintenance at early pregnancy through VPAC1 and VPAC2 receptors. VIP expression is induced in various cell types by growth factors and neurotransmitters and depends on CRE (cAMP responsive elements) and gp130 cytokine (CyRE) sites on its promoter. Here we investigated VIP/VPAC2 expression on first trimester cytotrophoblast cells (Swan-71 and HTR-8 cell lines) and the impact of VPAC2 overexpression or VIP silencing on trophoblast cell function and CRE-mediated signaling with special focus on migration and invasion. VIP expression was measured by flow cytometry and RT-qPCR; cell migration by wound healing assays and invasiveness in Matrigel-covered transwells. Trophoblast cells were transfected with X-tremeGENE HPDNA reagent with VPAC2 or CRE-Luciferase plasmids for 24h prior to the stimuli, normalized to GFP or b-gal. Endogenous VIP expression was detected in Swan71 and HTR8 cell lines and its synthesis was induced with 10nM VIP (P