Biomedical subjects

Ilana Goldberg-Cohen

Publications and source records attributed to Ilana Goldberg-Cohen.

3 recordsLinked to original sources

PubMed2006

Vascular cells.

Embryonic stem (ES) cells are cells derived from the inner cell mass of a blastocyst stage embryo. These self-renewing multipotent cells are able to differentiate to the three embryonic germ layers, the endoderm, ectoderm, and mesoderm, and are thus able to produce virtually all cell types. The ES cell capacity to generate various cell types has been studied extensively, and exploitation of ES cell characteristics allowed the production of several differentiated cell types of multiple tissues. Moreover, the process of ES cell differentiation provides a unique opportunity to observe early embryonic developmental events that are unattainable in the embryo itself. This chapter addresses the in vitro differentiation procedure of endothelial and vascular smooth muscle cells from human ES cells, with reference to similar studies performed in mouse and nonhuman primate ES cells, and provides several tools for the detailed characterization of differentiated cells.

Animals↗

PubMed2005

New horizons for VEGF. Is there a role for nuclear localization?

Angiogenesis, or new blood vessel formation, is a physiological response of tissues to hypoxia or ischemia. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that is up-regulated by hypoxia. The mechanisms responsible for hypoxic induction of VEGF are still not completely understood, though both transcriptional and post-transcriptional mechanisms are involved. In recent years, we have investigated cis-regulatory sequences and trans-acting factors which mediate the hypoxia-induced increase in VEGF mRNA stability. In particular, we have identified a 40 bp sequence motif in the 3'-untranslated region of VEGF mRNA, which is critical for the increase in VEGF mRNA stability with hypoxia and have shown that the RNA-binding protein, HuR, binds to this region. By means of indirect immunofluorescence experiments using monoclonal antibodies against HuR, we demonstrated that HuR localizes to the nucleus under hypoxia. As HuR binds to VEGF mRNA and appears to mediate stabilization of VEGF mRNA, it was of interest to show whether a fraction of VEGF protein localizes similarly to the nucleus. Double-labeling immunofluorescence showed that VEGF protein colocalizes with HuR in discrete nuclear compartments and nuclear VEGF protein was increased in hypoxia. These results indicate that VEGF may have a nuclear function, especially during hypoxia.

Active Transport, Cell Nucleus↗

PubMed2002

A 40-bp RNA element that mediates stabilization of vascular endothelial growth factor mRNA by HuR.

VEGF is a critical mediator of hypoxia-induced angiogenesis in numerous physiological and pathophysiological conditions. The hypoxic induction of VEGF is due in large part to an increase in the stability of its mRNA. We recently demonstrated that the stabilization of VEGF mRNA by hypoxia is dependent upon the RNA-binding protein HuR. This report describes the identification of a 40-bp functional HuR binding site in the VEGF mRNA 3'-untranslated region. This element can confer HuR-mediated stabilization of a heterologous gene in vitro and in vivo. Furthermore, the element is sufficient to confer an increase in the hypoxic induction of a heterologous gene. Deletion of the HuR binding site within this 40-bp element as mapped by RNase T1 and lead footprinting uncouples a stabilizing sequence from a destabilizing sequence, thus providing a novel RNA-protein regulatory model that might be exploited to manipulate VEGF expression and hypoxia-induced angiogenesis.

3' Untranslated Regions↗