NOVEL REGULATOR OF TRANSCRIPTION FACTOR AP-1 IN HUMAN TROPHOBLAST CELLS: FKBP52

ERLEJMAN A.G.; DE LEO S.A.; GARCIA G.A.; FONTANA V.; CAMISAY M.F.

CABA

Congreso; LXII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC) en el marco de la Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argenitna de Investigación Clínica

Abstract: The AP-1 family plays an importantrole en the regulation of fundamental trophoblast processes, including cellproliferation, differentiation and invasion. Alteration in a component of AP- 1,particulary c-fos protein, has been detected in placentas from preeclampsia(PE), as well as low protein level of FK506 binding protein 52 (FKBP52). FKBP52has been known by its role as cochaperone regulating others transcriptionfactors. The aim of this work was to analyze the effects of FKBP52 on AP-1signalling in trophoblast cells. BeWo cells were used as trophoblastic in vitromodel. Cells were transfected with wild type FKBP52 or its PPIase mutants, andthen, Stimulated by PMA. AP-1 signalling was evaluated by analyzing endogenousc-fos expression and stability (Western blot:WB), pERK/ERK ratio along time(WB) and c-fos sublocalization (immunofluorescence). AP-1 transcriptionalactivity was evaluated by luciferase assays and endogenous biological target asIL-6 secretion (ELISA) and MMP-2 proteolytic activity (zymography). In presenceof FKBP52, we observed a higher pERK/ ERK level for a longer time. Also wasdetected greater c-fos nuclear translocation, stability and protein abundance(1.9 ± 0,2 fold). Futhermore, FKBP52 stimulated AP-1 transcriptional activityon a concentration dependent manner (p<0.01, n=5). Besides, analyzing theeffects of these regulatory events, we observed an increased on IL-6 medium concentration(2,3 ± 0,3 fold) and MMP-2 enzymatic activity (2,5 ± 0,1 fold), abrogated bythe FKBP52 PPIase mutants. Conclusions: We demonstrated that FKBP52 modulatesdifferent points of AP-1 signalling, regulating the expression, sublocalizationand activity of target proteins. All in all, FKBP52 could be considered as apositive new regulator of AP-1 in trophoblast cells. Financial support: UBA, CONICETand PICT 2015-1603.Keywords:AP-1, c-fos, trophoblast cells, FKBP52