RESUMEN
Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell-cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels.
Asunto(s)
Angiomotinas , Células Endoteliales , Actinas/metabolismo , Cadherinas/metabolismo , Células Endoteliales/metabolismo , Humanos , Uniones Intercelulares/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAPRESUMEN
El cáncer de cérvix es una de las neoplasias diagnosticadas con más frecuencia durante la gestación. El manejo de estos casos será individualizado y basado en la edad gestacional en el momento del diagnóstico, el estadio tumoral y el deseo de la paciente de continuar o no con el embarazo. Presentamos el caso de un adenocarcinoma de cérvix diagnosticado en la semana 18 de gestación, en el que se decidió un manejo expectante (AU)
Cervical cancer is one of the most common malignancies diagnosed during pregnancy. The management of these patients is individualized and is based on gestational age at diagnosis, tumor stage, and the patient's desire to continue the pregnancy or not. We report a case of adenocarcinoma of the cervix that was diagnosed in the 18th week of pregnancy, in which the approach adopted was expectant management (AU)