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Nel presente studio è stato dimostrato come UPA non influenzi direttamente la migrazione delle cellule stromali endometriali e come, pertanto, non influisca sul riarrangiamento del citoscheletro di actina o sulle protrusioni di membrana, né inneschi la formazione di complessi di adesione focale o l’attivazione delle vie di segnalazione mediate da molecole correlate alle modifiche conformazionali e al movimento delle ESC come moesina o FAK. Quanto descritto si discosta da ciò che accade fisiologicamente in presenza di E2 e P4 i quali sono in grado di indurre la migrazione delle cellule stromali endometriali, il riarrangiamento del citoscheletro di actina e le protrusione di membrana, con la formazione di filopodi e lamellipodi, per mezzo della fosforilazione di Y397-FAK e T558-Moesina; tuttavia UPA, in combinazione con E2 o P4, è in grado di opporsi ai loro effetti stimolanti cosicché la molecola in questione è in grado di inibire indirettamente la migrazione delle ESC, il riarrangiamento del citoscheletro di actina e le protrusioni di membrana influenzando negativamente l’espressione di p-moesina e p-FAK.
In conclusione i risultati ottenuti forniscono indizi molecolari relativi alle modificazioni endometriali UPA-correlate mostrando come i PAECs potrebbero essere ricondotti ai peculiari effetti citoscheletrici indotti dalla molecola in questione sulle cellule stromali e, in particolare, all’interferenza con l’azione di E2 e P4. Inoltre, attraverso l’identificazione di quest’ultima correlazione, è possibile rafforzare l’idea che le modificazioni strutturali riscontrate nell’endometrio durante l’esposizione ad UPA non siano tanto correlate ad un’iperstimolazione cellulare quanto piuttosto alla possibilità di interferire con gli effetti estrogenici.
Queste informazioni contribuiscono alla prosecuzione della caratterizzazione dell’azione endometriale mediate da UPA e potrebbero rivelarsi utili per il potenziale impiego di questa molecola nel trattamento di condizioni nelle quali l’obiettivo è antagonizzare gli effetti estrogenici sull’endometrio come nel caso dell’endometriosi, dell’iperplasia o delle neoplasie endometriali.
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Ringraziamenti
Giunti al termine di questo lungo percorso sono molti i grazie che devo dispensare a tutti coloro che mi sono stati accanto in questi anni, seppur queste poche righe non riescano a riassumere la gratitudine per il sostegno ricevuto e la fiducia che mi è stata dimostrata.
Ringrazio il Prof. Tommaso Simoncini che mi ha permesso di frequentare il suo laboratorio e seguire il progetto da cui è scaturita questa tesi; ringrazio Magdalena e Jorge che fin da subito mi hanno fatta sentire accolta nel “nuovo mondo” del laboratorio accompagnandomi sino a questo traguardo.
Ringrazio la mia famiglia, soprattutto i miei genitori che hanno permesso, a ciò che era soltanto un sogno, di divenire una realtà, sostenendomi in ogni momento e dimostrandomi grande fiducia; ringrazio i miei fratelli, Michelangelo e Manuele, che mi hanno supportata ma, soprattutto, sopportata in questi anni ricchi di esami. Ringrazio nonna Emma che, con la sua ironia, ha sempre saputo alleggerire ogni momento di sconforto; ringrazio i miei zii, Giuseppe, Grazia, Laura e Lorenzo che, ciascuno a suo modo, hanno tifato per me in questi anni.
Ringrazio gli amici di una vita che hanno vissuto con me ogni tappa di questo percorso, in particolare un ringraziamento speciale va a Linda che, come una sorella, ha sorriso con me per ogni successo, ha saputo consolarmi ed ascoltarmi in ogni momento di difficoltà, spronarmi quando credevo di non potercela fare e incoraggiarmi con pazienza e dedizione.
Ringrazio Alessandro che, da vero compagno, ha condiviso con me in questi anni le gioie ed i “dolori” di questo percorso, ascoltando ogni preoccupazione e dimostrando grande pazienza e comprensione per i miei ritmi folli; ringrazio inoltre Romano, Cinzia, Lavinia e Federico che, come una seconda famiglia, hanno seguito le peripezie di questa avventura tifando sempre per me.
Ringrazio Chiara, il regalo più bello che questo lungo percorso universitario mi ha regalato, una compagna di studio brillante e tenace che ha saputo rendere meno faticose le sfide di questi anni, ma soprattutto un’amica sincera e generosa con cui ho avuto il piacere di condividere questo tratto di vita; ringrazio inoltre Patrizia e Viberto che, con le loro mille attenzioni e premure, mi hanno accolta nella loro famiglia facendomi sempre sentire come a casa nelle lunghe giornate di studio trascorse con Chiara.
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Ringrazio la fraternità di Marti della comunità Magnificat, con particolare riferimento alle sorelle “vecchie” e “nuove” della Piccola Comunità che in questi anni si sono sorbite con pazienza le mie condivisioni dimostrandomi grande affetto e sostegno.
Un pensiero speciale va anche a coloro che non potranno vedermi tagliare questo traguardo ma che sono stati sicuramente i miei più grandi sostenitori celesti, primi tra tutti i