Referencia

Cell Death and Differentiation advance online publication, 9 January 2015; doi:10.1038/cdd.2014.214

Autores

Fernandez-Alonso R.1*, Martin-Lopez, M.1*, Gonzalez-Cano L.1,+, Garcia- S.1, Castrillo F1., Diez-Prieto I.1,2, Fernandez-Corona A.1, 3, Lorenzo-Marcos ME.1,3, Li X.4, Claesson-Welsh L.4, Marques, M.M.5 & Marin, M.C.1** *Equal Contribution **Corresponding author: Dr. M.C. Marin, IBIOMED, Universidad de Leon, Campus de Vegazana, 24071 Leon, Spain. Tel: + 34-987-291793; e-mail: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo. | web: http://institutobiomedicina.unileon.es/ibmx_grupo10Eng.htm

Resumen

Vasculogenesis, the establishment of the vascular plexus and angiogenesis, branching of new vessels from the preexisting vasculature, involves coordinated endothelial differentiation, proliferation and migration. Disturbances in these coordinated processes may accompany diseases such as cancer. We hypothesized that the p53 family member p73, which regulates cell differentiation in several contexts, may be important in vascular development. We demonstrate that p73 deficiency perturbed vascular development in the mouse retina, decreasing vascular branching, density and stability. Furthermore, p73 deficiency could affect non endothelial cells (ECs) resulting in reduced in vivo proangiogenic milieu. Moreover, p73 functional inhibition, as well as p73 deficiency, hindered vessel sprouting, tubulogenesis and the assembly of vascular structures in mouse embryonic stem cell and induced pluripotent stem cell cultures. Therefore, p73 is necessary for EC biology and vasculogenesis and, in particular, that DNp73 regulates EC migration and tube formation capacity by regulation of expression of pro-angiogenic factors such as transforming growth factor-β and vascular endothelial growth factors. DNp73 expression is upregulated in the tumor environment, resulting in enhanced angiogenic potential of B16-F10 melanoma cells. Our results demonstrate, by the first time, that differential p73-isoform regulation is necessary for physiological vasculogenesis and angiogenesis and DNp73 overexpression becomes a positive advantage for tumor progression due to its pro-angiogenic capacity.

Descripción

En este artículo, publicado recientemente en Cell Death and Differentiation, estudiamos la función del gen TP73 en los procesos de vasculogénesis y angiogénesis tanto in vivo como in vitro. Para ello, utilizamos retinas de ratones neonatos y modelos de diferenciación endotelial en 2D y 3D a partir de células troncales embrionarias y células iPS. Demostramos que p73 regula estos procesos mediante la modulación de las vías de VEGF y TGFβ. Observamos que una de las isoformas de p73, DNp73, regula la migración de las células endoteliales e incrementa su potencial angiogénico. Consecuentemente, la expresión de esta isoforma se incrementa en el contexto del microambiente tumoral, lo cual contribuye a aumentar el potencial angiogénico del tumor. Nuestros datos demuestran, por primera vez, que la regulación diferencial del gen TP73 es un factor fundamental tanto en procesos fisiológicos de vasculogénesis y angiogénesis, como durante la angiogénesis y progresión tumoral.

grupo carmen marC3ADn 11

REFERENCIA DEL GRUPO INVESTIGADOR

Nuestro grupo, dirigido por la Dra. Carmen Marín y la Dra. Margarita Marqués Martínez, constituye el grupo de Diferenciación Celular y Diseño de Modelos Celulares integrado en el Instituto de Biomedicina (IBIOMED) de León. (http://institutobiomedicina.unileon.es/ibmx_grupo10.htm). Nuestra actividad investigadora se centra en identificar las interacciones funcionales de los genes que componen la familia de p53, en particular, p73 y p53, en la biología de las células troncales, en la organización de los nichos neurogénicos, la reprogramación celular y en los procesos de vasculogénesis y angiogénesis. Actualmente, Marta Martín López está finalizando su Tesis Doctoral sobre la función de p73 durante el proceso de reprogramación celular, y la Dra. Fernandez-Alonso es investigadora postdoctoral en el College of Life Sciences de la Universidad de Dundee.

Descárgate este artículo aquí.

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio al mejor artículo de jóvenes de la SEBBM, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature

01-11-2019

Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper...

Leer más

Self-Assembling ELR-Based Nanoparticles as Smart Drug-Delivery Systems Modulating Cellular Growth via Akt

01-10-2019

This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug delivery system based on elastin-like block recombinamers. The DNA recombinant technics allowed us to create...

Leer más

Structure–Function of MamC Loop and Its Effect on the *in Vitro* Precipitation of Biomimetic Magnetite Nanoparticles

01-09-2019

MamC, an integral protein of the magnetosome membrane, has recently been proposed as a strong candidate to produce biomimetic (magnetosome-like) magnetite nanoparticles that could be used as an alternative to...

Leer más

Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction

01-08-2019

Actinoporins are a group of soluble toxic proteins that bind to membranes containing sphingomyelin (SM) and oli- gomerize to form pores. Sticholysin II (StnII) is a member of the actinoporin...

Leer más

Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour

01-07-2019

To satisfy its high energetic demand, the brain depends on the metabolic cooperation of various cell types. For example, astrocytic-derived lactate sustains memory consolidation by serving both as an oxidizable...

Leer más

Glucose restriction promotes osteocyte specification by activating a PGC-1α-dependent transcriptional program

03-06-2019

Osteocytes, the most abundant of bone cells, differentiate while they remain buried within the bone matrix. This encasement limits their access to nutrients and likely affects their differentiation, a process...

Leer más

ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements

01-05-2019

/Bacillus subtilis/ ParB forms multimeric networks involving non-specific DNA binding leading to DNA condensation. Previously, we found that an excess of the free C-terminal domain (CTD) of ParB impeded DNA...

Leer más

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer

01-04-2019

Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New...

Leer más

p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton

01-03-2019

Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct...

Leer más

β‐RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice

01-02-2019

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In...

Leer más

Socios Protectores